• A high recurrence rate of non-Hodgkin's lymphoma (NHL) following chimeric antigen receptor T (CAR T) cell treatment remains a bottleneck, and immunosuppressive tumor microenvironment (TME) compromising CAR T cell efficacy in NHL is the primary cause of relapse. (bvsalud.org)
  • Here, we report a cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding the cavity to prevent GBM relapse. (nih.gov)
  • Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL), T cell receptor (TCR) and Chimeric Antigen Receptor (CAR) engineered T cells, or hematopoietic stem cell transplantation, is a promising new approach to cancer treatment. (nih.gov)
  • IL-2 and IFN-γ), immune checkpoint blockade (ICB) therapy (e.g., anti-PD-1/PD-L1 antibodies), and adoptive T-cell transfer (e.g., chimeric antigen receptor (CAR) T-cell therapy) [ 3 - 5 ]. (thno.org)
  • Hypoimmune anti-CD19 chimeric antigen receptor T cells provide lasting tumor control in fully immunocompetent allogeneic humanized mice. (ucsf.edu)
  • Induced pluripotent stem cell (iPSC)-derived macrophages (iMACs) are being used to make chimeric antigen receptor (CAR) macrophages for immunotherapy. (nature.com)
  • Moreover, the genetic engineering of macrophages with chimeric antigen receptor (CAR) allows them to recognize tumor antigens and perform tumor cell-specific phagocytosis. (springer.com)
  • Manufacture of chimeric antigen receptor (CAR)-T cells usually involves the use of viral delivery systems to achieve high transgene expression. (cartherics.com)
  • However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. (lu.se)
  • In addition, CXCL12 and CXCR4 are involved in antigen recognition by T and B cells and in shaping the tumor microenvironment (TME), mainly towards dampening immune responses. (unisr.it)
  • The CXCR4/CXCL12 axis plays a relevant role in shaping the tumor microenvironment (TME), mainly towards dampening immune responses. (unisr.it)
  • These CAR-MΦs were able to seek and engulf GSCs and clear residual GSCs by stimulating an adaptive antitumor immune response in the tumor microenvironment and prevented postoperative glioma relapse by inducing long-term antitumor immunity in mice. (nih.gov)
  • Accumulating research suggests that the tumor immune microenvironment (TIME) plays an essential role in regulation of tumor growth and metastasis. (biomedcentral.com)
  • Targeting tumor cells or the tumor microenvironment (TME) are the two major fundamental principles for antitumor therapies. (biomedcentral.com)
  • Different tumor types can also design their specific microenvironment by encouraging tumor angiogenesis and stimulating peripheral immune tolerance. (biomedcentral.com)
  • Regardless of the therapeutic approach, the heterogeneity of pancreatic cancer cells and the complexity of its tumor microenvironment contribute to the emergence of drug resistance. (frontiersin.org)
  • The microenvironment varies throughout a solid tumor with a tendency for central hypoxia and necrosis. (present5.com)
  • Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. (nature.com)
  • Furthermore, inflammatory mediators released by irradiated dying cells can attract and regulate immune cells in the tumor microenvironment (TME), further killing cancer cells. (nature.com)
  • Sulfatide could assist in recruiting NKT cells to the tumor, even if the lipids undergo minor changes in the tumor microenvironment. (cancer.gov)
  • However, increasing data has indicated that the clinical potential of most immunotherapies is usually hampered by immunosuppressive status of the tumor microenvironment (TME) [ 7 ]. (thno.org)
  • Multiple Injections of an Anti-CD47 Nanobody Fail to Achieve Total Blockade of CD47 in the Tumor Microenvironment. (nsdfu.org)
  • This creates a substantial antigen sink that sequesters A4 from your tumor microenvironment (3, 4). (nsdfu.org)
  • Once in the tumor microenvironment, proteases cleave and release one half of the functional block. (zymeworks.com)
  • Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). (encyclopedia.pub)
  • Background Macrophages expressing chimeric antigen receptors (CAR-M) have been shown to reduce tumor burden, remodel the tumor microenvironment (TME), and coordinate a systemic immune response in pre-clinical solid tumor models. (bmj.com)
  • In this Review article, as part of our Cancer Immunology and Immunotherapy series, the authors discuss these innovations and their application to study the tumor microenvironment. (nature.com)
  • Targeting macrophages to modulate the tumor immune microenvironment can ameliorate the tumor-associated immunosuppression and elicit an anti-tumor immune response. (springer.com)
  • A series of studies have revealed that exosomes-mediated intercellular transfer of proteins, nucleic acids, and metabolites plays a crucial role in the initiation and progression of HCC, hypoxia and angiogenesis, chemotherapy sensitivity, and cell death mode and regulates the immune microenvironment. (hindawi.com)
  • We laid particular focus on those researches that reveal how exosomes regulate the tumor immune microenvironment (TIME) and how exosomal cargos affect the progression of HCC. (hindawi.com)
  • HCC-derived exosomes participate in changing tumor progression by regulating the tumor microenvironment and tumor immune status [ 14 , 15 ]. (hindawi.com)
  • SIRPα-Fc-CD40L bound CD47 and CD40 with high affinity and activated CD40 signaling in the absence of Fc receptor cross-linking. (aacrjournals.org)
  • CD47 is a 50 kDa membrane receptor that has extracellular N-terminal IgV domain, five transmembrane domains, and a short C-terminal intracellular tail. (wikipedia.org)
  • CD47 is a high affinity receptor for thrombospondin-1 (TSP-1), a secreted glycoprotein that plays a role in vascular development and angiogenesis, and in this later capacity the TSP1-CD47 interaction inhibits nitric oxide signaling at multiple levels in vascular cells. (wikipedia.org)
  • CD47 interacts with signal-regulatory protein alpha (SIRPα), an inhibitory transmembrane receptor present on myeloid cells. (wikipedia.org)
  • Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. (bvsalud.org)
  • CXCR4 is a G-Protein coupled receptor that is expressed nearly ubiquitously and is known to control cell migration via its interaction with CXCL12, the most ancient chemokine. (unisr.it)
  • SRF231 exerts antitumor activity in vitro through both phagocytosis and cell loss of life in a way reliant on the activating Fc-gamma receptor (FcR), Compact disc32a. (nihvp.org)
  • High expression of CD47, a cell surface receptor on several types of cancer cells, has been identified as a 'don't eat me signal' that inhibits their killing by macrophages or NK cells. (nih.gov)
  • Breast cancer (BC)-initiating cells typically express high levels of CD44, a surface receptor for the extracellular matrix protein Hyaluronan, low levels of CD24, and exhibit high aldehyde dehydrogenase (ALDH) activity ( 3 ). (life-science-alliance.org)
  • The company's lead program, SL-172154 (SIRPα-Fc-CD40L), is designed to block the CD47 immune checkpoint and simultaneously activate the CD40 receptor, a member of the tumor necrosis factor superfamily, is being evaluated in multiple Phase 1 clinical trials. (shattucklabs.com)
  • BIT, an immune antigen receptor-like molecule in the brain. (medecinesciences.org)
  • The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. (medecinesciences.org)
  • All-hands on deck: Can we overcome the challenges associated with T cell receptor-based therapies? (asgct.org)
  • Roles for thrombospondin-1 signaling, mediated by specific cellular receptors or by activation of latent TGFß, have been defined in T and B lymphocytes, natural killer cells, macrophages, neutrophils, and dendritic cells. (bvsalud.org)
  • Pro-tumoral macrophages in lung tumors present a significant challenge in immunotherapy. (bvsalud.org)
  • Here, we introduce a pH-responsive nanomedicine approach for activating anti-tumoral macrophages and dendritic cells. (bvsalud.org)
  • Surface calreticulin activates macrophages and triggers dendritic cell maturation, promoting effective antigen presentation and therefore activating antitumor T cells. (bvsalud.org)
  • Herein, we engineered CD19-CAR T cells to secrete an anti-CD47 single-chain variable fragment (scFv) and validated their function in enhancing antitumor efficacy, regulating T cells differentiation, modifying phagocytosis and polarization of macrophages by in vitro and in vivo researches. (bvsalud.org)
  • Following the co-internalization of CXCR4 and CD47 in tumor cells, macrophages phagocytose them and cross-present their antigens to the adaptive immune system, leading to tumor rejection in a fraction of mice. (unisr.it)
  • Notably, CXCR4/CXCL12 cross-signal via the T and B cell receptors (TCR and BCR) and co-internalize with CD47, promoting tumor cell phagocytosis by macrophages in an anti-tumor immune process called ImmunoGenic Surrender (IGS). (unisr.it)
  • Several subsets of immune cells, including dendritic cells (DC) and macrophages are capable of serving as APCs. (labroots.com)
  • Wei X, Wang J, Liang M, Song M. Development of functional nanomedicines for tumor associated macrophages-focused cancer immunotherapy. (thno.org)
  • Clinical cancer immunotherapies are usually impeded by tumor immunosuppression driven by tumor associated macrophages (TAMs). (thno.org)
  • Of note, the TME is rich in immunosuppressive cells (e.g., tumor-associated macrophages (TAMs), regulatory T cells (Tregs), immature dendritic cells (iDCs) and myeloid-derived suppressor cells (MDSCs)), that can suppress antitumor immunity as a result of secretion of various cytokines and chemokines, which enables tumor escape from immune surveillance [ 8 ]. (thno.org)
  • Sloas C, Gabbasov R, Anderson N, Abramson S, Klichinsky M, Ohtani Y. 144 SIRPα deficient CAR-Macrophages exhibit enhanced anti-tumor function and bypass the CD47 immune checkpoint. (bmj.com)
  • They have previously shown in an LMS mouse model that inhibiting the CD47 protein allows immune cells called macrophages to more effectively destroy LMS cells. (sarcomahelp.org)
  • After secretion by the tumor cells, the CSF1 protein attracts macrophages and these macrophages can help the tumor to grow by helping to provide new blood vessels for the tumor. (sarcomahelp.org)
  • Macrophages, as one of the most abundant tumor-infiltrating cells, play an important role in tumor development and metastasis. (springer.com)
  • The frequency and polarization of tumor-associated macrophages (TAMs) correlate with disease progression, tumor metastasis, and resistance to various treatments. (springer.com)
  • Pro-inflammatory M1 macrophages hold the potential to engulf tumor cells. (springer.com)
  • In contrast, anti-inflammatory M2 macrophages, which are predominantly present in tumors, potentiate tumor progression and immune escape. (springer.com)
  • Besides, biomimetic carriers based on macrophages have been extensively explored to prolong circulation, enhance tumor-targeted delivery, and reduce the immunogenicity of therapeutics to augment therapeutic efficacy. (springer.com)
  • Herein, we introduce the role of macrophages in tumor progression, summarize the recent advances in macrophage-centered anticancer therapy, and discuss their challenges as well as future applications. (springer.com)
  • Solinas G, Germano G, Mantovani A, Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. (springer.com)
  • Komohara Y, Fujiwara Y, Ohnishi K, Takeya M. Tumor-associated macrophages: potential therapeutic targets for anti-cancer therapy. (springer.com)
  • Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer. (springer.com)
  • Yang QY, Guo NN, Zhou Y, Chen JJ, Wei QC, Han M. The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. (springer.com)
  • Because neutrophils and macrophages and have potent cytotoxic abilities we are examining whether it is possible to enlist this potential for tumour cell killing. (immunologyamsterdam.org)
  • We have demonstrated that macrophages are extremely efficient in phagocytosing and digesting circulating cancer cells in the presence of specific IgG mAbs. (immunologyamsterdam.org)
  • In lung tumor models in male mice, this combined approach shows anti-tumor effects and immunity against tumor re-exposure, highlighting its potential for lung cancer immunotherapy. (bvsalud.org)
  • Collectively, our research provides a more effective and safer CAR T cell transformation method for enhancing tumor immunotherapy. (bvsalud.org)
  • The complex interplay between cancer cells and the TIME influences the outcome of immunotherapy and other anticancer therapy (Fig. 1 ). (biomedcentral.com)
  • Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
  • Immune-inflamed tumors are called hot tumors, while the latter two are collectively referred to as cold tumors, and they respond poorly to immunotherapy. (nature.com)
  • One study reported an increased survival benefit with simultaneous RT compared with sequential administration, 8 while another study found no significant difference between the two strategies, 9 possibly because simultaneous RT plus immunotherapy and the administration of an ICI before RT may kill cancer cells as well a substantial number of immune cells, leading to poor systemic response and toxic side effects. (nature.com)
  • He hopes to elucidate what drives the immune system to fail to eliminate a tumor-and use those findings to therapeutically trigger the immune system to act more effectively against the tumor (an approach called immunotherapy). (cancer.gov)
  • Understanding how NKT cells can promote tumor infiltration is key to utilizing immunotherapy in brain tumors. (cancer.gov)
  • Because tumor immunity is driven by many immune system components that can either decrease or promote growth, NKT cells with specific lipid targets in the brain could be ideal mediators of immunotherapy to suppresses malignancy. (cancer.gov)
  • Immunotherapy is currently considered as a promising next-generation therapeutic strategy for various cancers thanks to its ability to modulate cell-specific immune responses toward tumors [ 1 ], which has gradually remodeled the landscape of clinical anticancer modality [ 2 ]. (thno.org)
  • Among most immunosuppressive cells, TAMs, as crucial drivers of immunosuppressive TME, account for the largest proportion of immune cells in the TME (approximately 50% of tumor mass) [ 9 , 10 ], which possess highly heterogeneity and play a complex regulatory role in tumor immunity and immunotherapy due to helping tumor evade immune surveillance [ 11 ]. (thno.org)
  • Moreover, TAMs usually display M2-like phenotypes that exert tumor-promoting role in TME, and promote production of related immunosuppressive factors that trigger immunotherapy resistance, including cytokines, chemokines, growth factors and soluble signaling mediators [ 12 ]. (thno.org)
  • Rocapuldencel-T is an autologous dendritic cell immunotherapy for patients with metastatic renal cell carcinoma about which we have written previously. (shu.edu)
  • Vaccine strategies for cancer immunotherapy depend on the induction of dendritic cells (DC) in close proximity to T cells. (shu.edu)
  • 4 xCELLigence real-time cell analysis 6 Diverse cancer immunotherapy applications 6 How does the xCELLigence real-time cell analysis assay work? (technologynetworks.com)
  • Various immunotherapy tumor-targeting schemes. (technologynetworks.com)
  • Here the authors review CAR T cell engineering and immunotherapy for cancer and juxtapose state-of-the-art developments with CAR NK cells as part of our Cancer Immunology series of Reviews. (nature.com)
  • Compared to viral-based methods, this method serves as an alternative and versatile way of generating T cells with tumor-targeting receptors for cancer immunotherapy. (cartherics.com)
  • Disrupting the binding of CD47 to SIRPα has emerged as a promising immunotherapeutic strategy for advanced cancers by potentiating antibody-dependent cellular phagocytosis (ADCP) of targeted antibodies. (aacrjournals.org)
  • Murine SIRPα-Fc-CD40L outperformed CD47 blocking and CD40 agonist antibodies in murine CT26 tumor models and synergized with immune checkpoint blockade of PD-1 and CTLA4. (aacrjournals.org)
  • Additionally, CD47 blocking antibodies inhibit proliferation of unstimulated astrocytoma cells but not normal astrocytes. (wikipedia.org)
  • However, apoptosis was not observed following culture with other anti-CD47 antibodies. (wikipedia.org)
  • Given the dose-limiting hematologic toxicity and antigen sink liability associated with current anti-CD47 antibodies in clinical development, Adagene has developed an anti-CD47 SAFEbody with precision masking for preferential binding on CD47 overexpressed on tumor versus normal cells. (adagene.com)
  • In xenograft models, directly thawed frozen FT536 significantly slowed tumor growth, which was further enhanced when infused in combination with the monoclonal antibodies. (sitcancer.org)
  • Cancer immunotherapies can be divided into four major categories: - Cytokines/immunomodulation agents - Monoclonal antibodies - Cell‑based therapies - Oncolytic viruses Though monoclonal antibodies currently represent the largest class of commercialized cancer immunotherapies, cell‑based therapies are rapidly making headway. (technologynetworks.com)
  • Throughout her career she has been fascinated by the role of antibodies in immunity and the activation of immune cells via antibody receptors (Fc receptors). (immunologyamsterdam.org)
  • Both myeloid cell types express Fc receptors and are, as such, able to recognize and kill tumour cells in the presence of specific monoclonal antibodies (mAbs) that opsonize tumour cells. (immunologyamsterdam.org)
  • By contrast, neutrophils induce tumour cell death especially in the presence of monoclonal antibodies of the IgA subclass. (immunologyamsterdam.org)
  • Jurkat cells and peripheral blood mononuclear cells (PBMC) incubated with the monoclonal antibody Ad22 results in apoptosis within 3 hours. (wikipedia.org)
  • Treatment with a disulfide-linked antibody dimer induces apoptosis of CD47-positive primary B-CLL and leukemic cells (MOLT-4 and JOK-1). (wikipedia.org)
  • In addition, administration of the antibody prolonged survival of SCID mice implanted with JOK-1 cells. (wikipedia.org)
  • The drug candidate is a recombinant, humanized bi-specific monoclonal antibody acts by targeting leukocyte surface antigen CD47 and programmed cell death Ligand 1 (PD L1). (pharmaceutical-technology.com)
  • Immunotherapies with antibody-drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. (lu.se)
  • The efficacy was analogous or preferable to the combination of CAR T cells and CD47 antibody. (bvsalud.org)
  • Furthermore, locally delivering anti-CD47 by CAR T cells potentially limits toxicities relevant to systemic antibody treatment. (bvsalud.org)
  • In an orthotopic patient-derived glioblastoma humanized mouse model, the combined treatment with nanoporter-hydrogel superstructure and CD47 antibody increased the frequency of positive immune responding cells and suppressed the negative immune regulating cells, conferring a robust tumoricidal immunity surrounding the postsurgical cavity and inhibiting postoperative glioblastoma relapse. (nih.gov)
  • Conversely, the CD47 antibody B6H12 that blocks SIRPα binding enhances macrophage-dependent clearance of tumors in several mouse models, although others have shown that such clearance can be independent of SIRPα signaling. (nih.gov)
  • SAN DIEGO and SUZHOU, China, December 13, 2021 - Adagene Inc. ("Adagene") (Nasdaq: ADAG), a biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, today announced preclinical data demonstrating the compelling differentiation of ADG153, an anti-CD47 monoclonal antibody (mAb), and ADG152, a CD20xCD3 bispecific T-cell engager (TCE). (adagene.com)
  • Our novel anti-CD47 antibody and CD20xCD3 bispecific TCE programs successfully leverage SAFEbody technology for precision masking to decouple efficacy from the toxicities that are often associated with therapeutic modalities for these two important targets on the forefront of clinical development for hematologic malignancies," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. (adagene.com)
  • Our first POWERbody CD20xCD3 bispecific TCE with precision masking on our tailor-made anti-CD3 arm is highly differentiated, engineered for potent and sustained tumor killing with more than 100-fold cytokine release control and 2-3-fold prolonged half-life in comparison with a benchmarked antibody in clinical development. (adagene.com)
  • ADG153-G4 parental antibody and its activated SAFEbody can block the CD47 signal by targeting a unique epitope of CD47 with high affinity and minimal RBC hemagglutination. (adagene.com)
  • We recently reported that AO-176, a clinical stage humanized anti-CD47 IgG2 antibody, possesses differentiated characteristics such as preferential binding of tumor cells compared to normal cells, a lack of binding to red blood cells, non-ADCC direct tumor killing and elicits immunogenic cell death with DAMP induction, all in addition to single-agent phagocytosis. (netlify.app)
  • Bryan Hancock, PhD (Fate Therapeutics) previewed the preclinical studies supporting the investigational new drug application for FT536, a CAR NK cell product derived from an inducible pluripotent stem-cell line engineered for enhanced effector cell functionality, persistence, and multi-antigen targeting capabilities through CD16-mediated antibody dependent cellular cytotoxicity (ADCC). (sitcancer.org)
  • Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression. (ucsf.edu)
  • The mouse monoclonal antibody 5E10 recognizes CD90/Thy-1, a GPI-anchored cell surface glycoprotein expressed predominantly on thymocytes, hematopoietic stem cells and neurons. (exbio.cz)
  • DSP107 targets CD47-overexpressing tumors, simultaneously blocking macrophage inhibitory signals and delivering an immune costimulatory signal to tumor antigen-specific activated T-cells. (pharmiweb.com)
  • These activities lead to targeted immune activation through both macrophage and T-cell mediated tumor destruction. (pharmiweb.com)
  • These data illustrated that whereas CD47/SIRPα inhibition could potentiate tumor cell phagocytosis, CD40-mediated activation of a type I interferon response provided a bridge between macrophage- and T-cell-mediated immunity that significantly enhanced durable tumor control and rejection. (aacrjournals.org)
  • The antiphagocytic activity of CD47/SIRPα serves as a macrophage checkpoint or "do not eat me" signal ( 1 ). (aacrjournals.org)
  • CD47 has been proved to be a promising therapeutic target and is crucial in regulating macrophage function. (bvsalud.org)
  • While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. (bvsalud.org)
  • Through its Fc domains, SRF231 engagement with macrophage-derived Compact disc32a acts dual reasons by eliciting FcR-mediated phagocytosis of cancers cells and performing being a scaffold to operate a FLJ14936 vehicle Compact disc47-mediated loss of life signaling into tumor cells. (nihvp.org)
  • In tumor-bearing mice, SRF231 boosts tumor macrophage infiltration and induction from the macrophage cytokines, mouse chemoattractant proteins 1 and macrophage inflammatory proteins 1 alpha. (nihvp.org)
  • In mice bearing brain metastatic 4T1br3 tumors, anti-CD47 treatment shrank tumors by roughly 50% compared to controls, which accompanied by a 5-fold increase in expression of F4/80 macrophage markers in the tumors. (sitcancer.org)
  • Solid tumors overexpress immunosuppressive molecules, such as CD47, which reduces macrophage tumor phagocytosis. (bmj.com)
  • Vignery A. Macrophage multinucleation is accompanied by the expression of new soluble and membrane antigens in mice. (medecinesciences.org)
  • Vignery A. Osteoclasts and giant cells: macrophage-macrophage fusion mechanism. (medecinesciences.org)
  • CD47, a ligand for MFR, participates in macrophage multinucleation. (medecinesciences.org)
  • Zhou XF, Liu XR, Huang L. Macrophage-mediated tumor cell phagocytosis: opportunity for nanomedicine intervention. (springer.com)
  • We are currently investigating the mechanisms of neutrophil- and macrophage mediated tumour cell killing in more detail, as we anticipate that this knowledge will help us to develop novel (pre-operative) adjuvant anti-cancer therapies. (immunologyamsterdam.org)
  • The CD47/SIRPα interaction leads to bidirectional signaling, resulting in different cell-to-cell responses including inhibition of phagocytosis, stimulation of cell-cell fusion, and T-cell activation. (wikipedia.org)
  • Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. (bvsalud.org)
  • SRF231 binds to individual Compact disc47 particularly, blocks the Compact disc47/SIRP connections and network marketing leads to induction of tumor cell phagocytosis and tumor-intrinsic cell loss of life. (nihvp.org)
  • The anti-tumor efficacy of CAR-M in vitro was monitored by quantifying killing, phagocytosis, and cytokine production in co-culture assays with HER2+ tumor cell lines. (bmj.com)
  • Compared to unmodified CAR-M, SIRPα-knockdown CAR-M exhibited enhanced killing, phagocytosis, and cytokine production against HER2+ tumor cells in vitro . (bmj.com)
  • 6MW-3211 is under development for the treatment of advanced malignancy tumors, relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), extensive-stage small cell lung cancer, non-small cell lung cancer, relapsed and refractory lymphoma and renal cell carcinoma and solid tumor. (pharmaceutical-technology.com)
  • The in vivo efficacy of CAR-M was characterized using metastatic solid tumor xenograft models. (bmj.com)
  • Indeed, CAR-T cells were found to be potent killers of 3D solid tumor cell culture models. (cartherics.com)
  • Thrombospondin-1 is a secreted matricellular glycoprotein that modulates cell behavior by interacting with components of the extracellular matrix and with several cell surface receptors. (bvsalud.org)
  • In addition to regulating physiological nitric oxide signaling and responses of cells to stress, studies in mice lacking thrombospondin-1 or its receptors have revealed important roles for thrombospondin-1 in regulating immune responses in infectious and autoimmune diseases and antitumor immunity. (bvsalud.org)
  • Simple Summary Chemokines are small soluble proteins that control and regulate cell trafficking within and between tissues by binding to their receptors. (unisr.it)
  • Here, the authors show that combining γ9δ2 TCR-mediated metabolic and co-stimulatory stress targeting by chimeric NKG2D or anti-CD277 co-receptors shapes transcriptomic heterogeneity of engineered T cells and is associated with improved control of solid tumors. (nature.com)
  • CD47 is overexpressed on many cancer cells and binds SIRPα on immune phagocytic cells to produce a "don't eat me" signal. (pharmiweb.com)
  • The CD47/SIRPα pathway is an endogenous pathway that facilitates clearance of aged or dying cells ( 1 ). (aacrjournals.org)
  • CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). (wikipedia.org)
  • The company's SL-172154 (SIRPα-Fc-CD40L) program, which is designed to block the CD47 immune checkpoint and simultaneously agonize the CD40 pathway, is being evaluated in two Phase 1 trials. (canadianinsider.com)
  • We have previously demonstrated that CD47 is a checkpoint that reduces CAR-M function, and have shown that CRISPR-mediated SIRPα knockout (KO) CAR-M are refractory to the anti-phagocytic checkpoint protein CD47. (bmj.com)
  • Furthermore, SIRPα-knockdown CAR-M significantly delayed tumor growth and prolonged survival in vivo . (bmj.com)
  • Conclusions We show the feasibility of generating gene-silenced primary CAR-M in a single transduction step by integrating CAR delivery with custom intronic shRNA, and we demonstrate that targeted gene knockdown of SIRPα can enhance the anti-tumor activity of CAR-M in vivo . (bmj.com)
  • Cloning of two members of the SIRP alpha family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells. (medecinesciences.org)
  • SIRPγ (CD172g) binds to CD47 (integrin-associated protein/IAP) that is widely expressed on most hematopoietic cells, epithelial cells, endothelial cells, fibroblasts and many tumor cell lines. (bdbiosciences.com)
  • SIRPγ (CD172g) may play a regulatory role in T cell-T cell interactions and may induce apoptosis through CD47. (bdbiosciences.com)
  • CD47 (Cluster of Differentiation 47) also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. (wikipedia.org)
  • CD47 ( C luster of D ifferentiation 47) also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene . (wikidoc.org)
  • The cellular and molecular nature of the TIME influences cancer progression and metastasis by altering the ratio of immune- suppressive versus cytotoxic responses in the vicinity of the tumor. (biomedcentral.com)
  • These tumors and accessories represent the hallmark characteristics that support tumor progression and lead to metastasis. (biomedcentral.com)
  • The ratio of pro- to antitumor immune populations in the TIME plays a critical role in the regulation of tumor progression and metastasis. (biomedcentral.com)
  • The crosstalk between pro-tumorigenic immune cells, stromal cells, and cytokines helps to establish the pre-metastatic niche for disseminated circulatory tumor cells and facilitates metastasis. (biomedcentral.com)
  • The processes of tumor initiation, expansion, and metastasis are governed by the TIME, where immunosuppressive and antitumor immune crosstalk play an important role. (biomedcentral.com)
  • During metastasis, tumor-derived exosomes help in the requirement and arrangement of immunosuppressive immune cells for favorable premetastatic niche formation and growth of metastases. (biomedcentral.com)
  • Moreover, single-cell sequencing provides unique insights into the mechanisms of pancreatic cancer metastasis and cachexia, paving the way for developing novel preventive strategies. (frontiersin.org)
  • It unlocks novel dimensions by uncovering elusive cell populations and tumor heterogeneities for early detection, unraveling mechanisms of treatment resistance, tailoring therapies to individuals, and illuminating metastasis and cachexia pathways, thereby opening fresh avenues for preventive strategies. (frontiersin.org)
  • Introduction Cancer may be considered to be an unregulated proliferation of cells of which the cardinal features in addition to growth are invasion and metastasis. (present5.com)
  • Cancer stem cells (CSCs) are implicated in tumor initiation, metastasis and drug resistance, and considered as attractive targets for cancer therapy. (life-science-alliance.org)
  • Tumour cell hybridization and metastasis revisited. (medecinesciences.org)
  • Muc1 promotes migration and lung metastasis of melanoma cells. (ajcr.us)
  • Lewis Y antigen modified CD47 is an independent risk factor for poor prognosis and promotes early ovarian cancer metastasis. (ajcr.us)
  • A number of studies have proved that exosomes are important mediators for the initiation, progression, angiogenesis, and metastasis of tumors [ 10 ]. (hindawi.com)
  • Therefore, our work establishes a locoregional treatment strategy for priming cancer stem cell-specific tumoricidal immunity with broad application in patients suffering from recurrent malignancies. (nih.gov)
  • Finally, because NKT cells have an innate response component and are often referred to as innate T-lymphocytes, Dr. Terabe's team hopes to elucidate the mechanisms behind tumor immunity in glioblastoma with a specific focus on NKT cells. (cancer.gov)
  • Tumor immunogenicity results from the processing, and subsequent presentation of tumor antigens released from dead or dying tumor cells on MHC molecules expressed on antigen-presenting cells (APC). (aacrjournals.org)
  • In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. (nature.com)
  • The rationale of this approach is to bypass mechanisms by which cancer cells dampen the anti-tumor immune response, including down-regulation of MHC Class I molecules. (shu.edu)
  • In a study of lung adenocarcinoma [ 4 ] , EMT markers were associated with enhanced tumor infiltration of CD4 + Foxp3 + Tregs and upregulation of inhibitory immune checkpoint molecules such as programmed cell death (PD)-ligand (L) 1, PD-L2, TIM-3, B7-H3, and CTLA-4. (encyclopedia.pub)
  • Thus, a high expression of inhibitory immune checkpoint molecules such as PD-1, PD-L1, CTLA-4, OX40L, and PD-L2 was observed in tumors with the most mesenchymal EMT scores. (encyclopedia.pub)
  • Proceeds will be used for advancing the Company's next generation immuno-oncology drug candidates including the clinical development of the Company's lead product, DSP107, an anti-CD47 therapy for the treatment of solid tumors through a Phase I/II study and the preclinical advancement of additional pipeline projects. (pharmiweb.com)
  • Inhibition of Growth Experimental cancer chemotherapy has been largely directed at the inhibition of cellular proliferation with little attention being directed to more difficult models which would detect effects on the invasive and metastatic potential of cancer cells. (present5.com)
  • This subpopulation of cells, also known as tumor-initiating cells (TICs), are commonly associated with drug-resistance and metastatic potential, and are considered as promising targets for therapeutic intervention. (life-science-alliance.org)
  • Patient biopsies revealed an 89% increase in CD47 expression by immunohistochemistry in metastatic brain TNBC tumors compared to primary lesions. (sitcancer.org)
  • Knockout of CD47 led to 60% increased survival and 89% decreased metastatic brain lesions in 4T1-bearing mice compared to controls. (sitcancer.org)
  • These strategies will expand the toolkit for treating tumors, especially for solid tumors, drug-resistant tumors, and metastatic tumors. (springer.com)
  • MOL2-13-185-s002.xlsx (83K) GUID:?3750B82C-9E1B-45CD-8C52-A12703E7D2A9 Abstract The peritoneal fluid of ovarian carcinoma patients promotes cancer cell invasion and metastatic spread with lysophosphatidic acid (LPA) like a potentially crucial mediator. (ece-inhibitor.com)
  • As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. (lu.se)
  • Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. (medecinesciences.org)
  • 4 According to the number of tumor-infiltrating lymphocytes, tumors can be divided into three phenotypes: immune-inflamed, immune-excluded, and immune-desert types. (nature.com)
  • While there are various types of T-lymphocytes, NKT cells stand out for a few reasons. (cancer.gov)
  • Most of them generally follow the same pathway to make immune-activated cytotoxic T lymphocytes (CTLs) abundantly infiltrate into tumor tissues and destroy tumor cells [ 6 ]. (thno.org)
  • In this mesenchymal subtype, a decreased number of CD8 + tumor-infiltrating lymphocytes (TILs) were detected, suggesting an association between EMT tumor cells and exclusion of these immune cells from the TME. (encyclopedia.pub)
  • Signal-regulatory protein alpha (SIRPalpha) but not SIRPbeta is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34(+)CD38(-) hematopoietic cells. (exbio.cz)
  • Binding of TSP-1 to CD47 influences several fundamental cellular functions including cell migration and adhesion, cell proliferation or apoptosis, and plays a role in the regulation of angiogenesis and inflammation. (wikipedia.org)
  • While many methods have been developed to screen and evaluate the efficacy of immune cell‑mediated killing, there is a need for a more robust in vitro assay to accurately predict the in vivo behavior of therapies. (technologynetworks.com)
  • While the data provided by these assays help piece together an understanding of different facets of immune cell‑mediated killing, it is important to note that the parameters being reported often do not correlate with target cell killing efficacy in vivo. (technologynetworks.com)
  • Approaches to improve therapy barriers include selecting appropriate CAR-T cell targets, ideally with low expression on healthy cells and engineering CAR-T cells with multiple targets using different 'logic-gate' strategies tailored to strike the balance between the safety and efficacy of the therapy. (cartherics.com)
  • Unlike microbial chemotherapy in which there are marked differences in chemistry from the host cells, the cancer cell provides relatively limited changes from the normal cells and does not offer clear targets for chemotherapeutic attack. (present5.com)
  • The intronic shRNA design is a generalizable platform that will be valuable for future CAR designs, target tumor antigens, and gene knockout targets. (bmj.com)
  • In this two-year study, Dr. van de Rijn and Santosh Gupta, PhD aim to determine whether three proteins that are expressed at various levels in LMS tumors can be used as targets for novel therapies. (sarcomahelp.org)
  • Published in Frontiers in Immunology ( https://doi.org/10.3389/fimmu.2022.968395 ), Van To and colleagues review the current potential CAR-T cell targets for Cutaneous T cell lymphoma (CTCL), and the strategies required for more effective treatment of the disease. (cartherics.com)
  • Other cell surface proteins, including CD326 (EpCAM), epithelial specific antigen, CD133, CD166, CD47, CD201, and ABCG2 have been reported as CSC markers for different BC subtypes and drug-resistant tumors ( 4 , 5 ). (life-science-alliance.org)
  • Multiple studies have shown that CSCs have the capacity to regenerate bulk tumors that are mostly composed of non-cancer stem cells (NCSCs) ( 8 ), whereas NCSCs can dedifferentiate and acquire a CSC phenotype upon epithelial mesenchymal transition (EMT) ( 9 ). (life-science-alliance.org)
  • An association between EMT tumor cells (mesenchymal and hybrid epithelial-mesenchymal phenotypes) and increased numbers of infiltrating PD-1 + cells was also observed in another study in patients with adenocarcinoma of the lung [ 6 ] . (encyclopedia.pub)
  • CD47 interacts with several membrane integrins, most commonly integrin αVβ3. (wikipedia.org)
  • It is likely that intracellular and membrane-associated partners are crucial in determining the cellular response of CD47 signaling. (wikipedia.org)
  • CD47 interacts with several membrane integrins, most commonly integrin avb3. (wikidoc.org)
  • A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. (medecinesciences.org)
  • The most commonly used method for measuring immune cell‑mediated killing is the release assay, where effector cell‑mediated disruption of the target cell membrane results in leakage of its cytoplasmic contents into the culture medium. (technologynetworks.com)
  • CD90 (Thy-1) is an 18-35 kDa GPI-anchored plasma membrane glycoprotein expressed in many cell types, such as in hematopoietic cells and neurons, connective tissues, various fibroblast and stromal cell lines, tumor endothelial cell lines and other. (exbio.cz)
  • If the cancer antigens are presented on licensed dendritic cells, logically, the immune system would be appropriately stimulated to attack the cancer. (shu.edu)
  • These observations underscore the potential clinical benefit of AXL inhibition/down-regulation in drug-resistant tumors, which commonly display EMT properties and are enriched in CSCs ( 18 ). (life-science-alliance.org)
  • In vivo focusing on of CD47 poses challenging due to its higher level of manifestation on cells of hematopoietic source, including red blood cells (RBCs) and platelets. (nsdfu.org)
  • Daily doses of 200 g of A4 stained 50C60% of accessible CD47 on circulating hematopoietic cells (3, 4, 7, 10). (nsdfu.org)
  • Sharpe and colleagues devise a conditional gene deletion model in mice for rapid sequential, combinatorial and lineage-specific interrogation of gene function in hematopoietic cells. (nature.com)
  • The first poster will highlight preclinical data from the company's GADLEN™ platform, while the second will highlight preclinical data from SL-9258 (TIGIT-Fc-LIGHT), derived from the company's ARC ® platform, demonstrating its ability to broaden the activity of checkpoint inhibitors through targeted myeloid cell and effector lymphocyte activation. (canadianinsider.com)
  • With PROgrammed Tumor Engagement and Checkpoint/Co‑stimulation Targeting, our ProTECT™ technology delivers multifunctional tumor-specific activity while simultaneously enhancing immune modulation through the conditional activity of a natural immunomodulatory pair such as PD-1/PD-L1. (zymeworks.com)
  • Synthetic immune checkpoint engagers protect HLA-deficient iPSCs and derivatives from innate immune cell cytotoxicity. (ucsf.edu)
  • While tumor expansion, contact-dependent or independent crosstalk between tumor and TIME affects the production of various cytokines that help in the polarization of antitumor immune response in the immunosuppressive TIME. (biomedcentral.com)
  • In the tumor acidic environment, TTA-Q6 is released, disrupting cancer cell calcium uptake, causing endoplasmic reticulum stress and inducing calreticulin transfer to the cell surface. (bvsalud.org)
  • Simultaneously, RRX-001 reduces CD47 protein levels, aiding in preventing immune escape by calreticulin-rich cancer cells. (bvsalud.org)
  • Therefore, understanding the TME and its immune cell components are equally important as cancer cell characteristics for tumor eradication. (biomedcentral.com)
  • Tumor-infiltrating immune cells are an important component of the TIME and are a significant predictor of cancer patients' survival. (biomedcentral.com)
  • During the tumor initiation stage, cancer cells escape from immune surveillance. (biomedcentral.com)
  • Overall, single-cell sequencing has immense potential in promoting early diagnosis, guiding personalized treatment, and preventing complications of pancreatic cancer. (frontiersin.org)
  • Emerging single-cell sequencing technologies will undoubtedly enhance our understanding of the complex biology of pancreatic cancer and pave the way for new directions in its clinical diagnosis and treatment. (frontiersin.org)
  • Applications of single-cell sequencing technology in the diagnosis and treatment of pancreatic cancer. (frontiersin.org)
  • Single-cell sequencing technology transforms the landscape of pancreatic cancer diagnosis and therapy. (frontiersin.org)
  • Additionally, the company is advancing a proprietary Gamma Delta T Cell Engager, GADLEN™, platform, which is designed to bridge gamma delta T cells to tumor antigens for the treatment of patients with cancer. (canadianinsider.com)
  • Since there is generally negligible immune response to cancer cells it has been argued that there should be complete elimination of neoplastic cells for a cure to be achieved. (present5.com)
  • There is experimental evidence that a single cancer cell may be sufficient to give rise to a fatal response after proliferation. (present5.com)
  • Further evidence suggests that a given dose of a cancer chemotherapeutic agent causes the death of a constant proportion of cancer cells (first order kinetics). (present5.com)
  • For this reason, the elimination of all cancer cells is more likely to be achieved when the tumor burden is small. (present5.com)
  • The objectives in combination chemotherapy have been to limit the toxicity of individual agents and to evade drug resistance by exposing the cancer cell to drugs with different modes of action simultaneously. (present5.com)
  • Toxicity of Anticancer Drugs The therapeutic index for cancer chemotherapeutic agents is usually low and the cells of the bone marrow and the gastrointestinal tract are usually the most sensitive normal cells. (present5.com)
  • RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
  • RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)
  • Dr. Terabe hopes to translate his knowledge on NKT cells to new cancer treatments that can help patients combat brain tumors more effectively. (cancer.gov)
  • ACT harnesses an individual's adaptive immune system to fight against cancer, with fewer side-effects and more specific anti-tumor activity. (nih.gov)
  • Despite their promise of ACT as curative, these therapies are often limited by the persistence and robustness of the responses of the T cells to the cancer cells. (nih.gov)
  • ProTECT™ can change and stop how cancer cells communicate, use or hide from your immune system to grow. (zymeworks.com)
  • Several companies, including Trillium , Celgene , Tioma, and Forty Seven are developing products that block CD47 for the treatment of cancer. (shu.edu)
  • AXL, PYK2, and PKCα expression correlates with stemness signature in basal-like breast cancer patients, and their depletion in multiple mesenchymal TNBC cell lines markedly reduced the number of mammosphere-forming cells and cells harboring CSCs characteristic markers. (life-science-alliance.org)
  • Cancer stem cells (CSCs) represent a small fraction of cancer cells, characterized by specific cellular markers, self-renewal and tumor-initiating capacities ( 1 , 2 ). (life-science-alliance.org)
  • Compounds derived from our GADLEN platform represent a novel approach to targeting gamma delta t-cells and are designed to bridge gamma delta T cells to tumor antigens for the treatment of cancer. (shattucklabs.com)
  • Jessica D. Mackert, PhD (Wake Forest University) described preclinical data supporting CD47 as a target for the treatment of brain metastases in triple-negative breast cancer (TNBC). (sitcancer.org)
  • Persistent increases in serum levels of interferon gamma and granzyme B were observed in both Arms (6/20 patients in Arm 4 and 2/20 patients in Arm B). These data suggest that the generation of tumor-antigen-specific T cells through vaccination may help overcome primary resistance to anti-PD-1 monotherapy in prostate cancer. (sitcancer.org)
  • Her research has redefined the molecular map of breast cancer and led to new paradigms in understanding how human tumors evolve and metastasize. (stanford.edu)
  • This class of personalized therapies involves collecting immune cells from an individual, engineering them to recognize and kill cancer cells, before culturing, and reintroducing them into the same individual. (technologynetworks.com)
  • Both chemotherapy and radiation therapy have from the onset been focused on killing cancer cells, in one case by using highly toxic chemicals and in the other case by using focused radiation. (anti-agingfirewalls.com)
  • And d) Another very basic problem is that cancer cells tend to be remarkably clever and naturally seek to take advantage of numerous cellular survival mechanisms to stay alive under stress, for example by upregulating heat shock proteins or DNA repair mechanisms. (anti-agingfirewalls.com)
  • These concerns have led to the development of ever-smarter treatments, ones more targeted or that takes advantage of molecular vulnerabilities of cancer cells. (anti-agingfirewalls.com)
  • This blog entry is concerned with another "smart" approach: simultaneously targeting multiple molecular pathways in cancer cells to defeat their protective responses. (anti-agingfirewalls.com)
  • A very large number of gene mutations may be involved in a single cancer - 50 or more - making the molecular dynamics of cancer cells different in important respects from those of normal cells. (anti-agingfirewalls.com)
  • Beclin-1-independent autophagy mediates programmed cancer cell death through interplays with endoplasmic reticulum and/or mitochondria in colbat chloride-induced hypoxia. (ajcr.us)
  • LIN28B suppresses microRNA let-7b expression to promote CD44+/LIN28B+ human pancreatic cancer stem cell proliferation and invasion. (ajcr.us)
  • 3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells. (ajcr.us)
  • Up-regulated CKS2 promotes tumor progression and predicts a poor prognosis in human colorectal cancer. (ajcr.us)
  • MicroRNA-320a inhibits proliferation and invasion of breast cancer cells by targeting RAB11A. (ajcr.us)
  • MiR-449a suppresses cell invasion by inhibiting MAP2K1 in non-small cell lung cancer. (ajcr.us)
  • CTCL is a blood cancer caused by malignant T cells. (cartherics.com)
  • These are associated with the creation and application of the therapy, as well as the cancer cell environment. (cartherics.com)
  • CAR-T cells are engineered to identify a pre-determined target on cancer T cells. (cartherics.com)
  • Cancer cells can also reduce their expression of the target, which may lead to therapy resistance, and during the manufacture of CAR-T cells from patient blood, the therapy may become contaminated with cancerous cells. (cartherics.com)
  • CAR-T cell therapy aims to target and kill cancer cells, and boost a patient's immune system to fight cancer. (cartherics.com)
  • Solid cancers are able to create an environment that supports cancer growth and 'protects' cancer cells from elimination. (cartherics.com)
  • When CAR-T cells are exposed to this complex environment for an extended time their ability to kill cancer cells can be reduced. (cartherics.com)
  • Designing a delivery system that shields CAR-T cells from the impact of the cancer environment may improve outcomes of CAR-T therapy in solid cancers. (cartherics.com)
  • Importantly, encapsulation in microgel carriers did not impact their ability to kill cancer cells. (cartherics.com)
  • Of note, anti-CD47 scFv secreting CAR T cells exert a more potent immune response following specific antigen stimulation compared with parental CAR T cells, characterized by more efficient degranulation and cytokine production with polyfunctionality. (bvsalud.org)
  • NKT cells have been known to specifically target lipids, which can undergo changes in expression upon tumor development and progression in various cancers. (cancer.gov)
  • New research shows that an imbalanced response - driven partially by the productive infection of antigen-presenting cells - is associated with progression to severe disease. (nature.com)
  • Up regulation of the long non-coding RNA NEAT1 promotes esophageal squamous cell carcinomacell progression and correlates with poor prognosis. (ajcr.us)
  • In this paper, we reviewed the recent researches on the multiple roles of tumor-associated exosomes in the progression of HCC. (hindawi.com)
  • CD3ε FP T cells were predominantly CD8+ effector memory T cells, and exhibited anti-tumor activity in vitro and in vivo. (cartherics.com)
  • The "don't eat me signal" CD47 is a pleitropic surface marker expressed on numerous cell types that inhibits myeloid cell phagocytic activity through binding SIRPalpha as well as an antagonizes T cell function mediated by interaction with matricellular protein Thrombospondin-1. (sitcancer.org)
  • His research currently focuses on natural killer T (NKT) cells, a lesser-known component of the immune system with the response rate of the innate immune system but the antigen specificity of the adaptive immune system. (cancer.gov)
  • Second, NKT cells mount a response as quickly as the innate immune system, while retaining the antigen specificity of T-cells in the adaptive immune system. (cancer.gov)
  • Pulendran and colleagues delineated the mechanisms underlying the nonspecific antiviral effects exerted by the BCG vaccine against SARS-CoV-2 and reveal a pivotal role for BCG-specific CD4 + T cells that produce interferon-γ in imprinting a persistent antiviral innate program in the lung, mediating heterologous viral protection. (nature.com)
  • The emergence of multifunctional nanomaterials can expectedly endow these therapeutic cargoes with high solubility, favorable pharmacokinetic distribution, cell-specific delivery, and controlled release. (thno.org)
  • Using a layered double hydroxide nanosheet carrier, we co-deliver a T-type calcium channel inhibitor (TTA-Q6) and a CD47 inhibitor (RRX-001) into lung tumors. (bvsalud.org)
  • The company concluded that its investigational CD47 inhibitor was unlikely to demonstrate a survival benefit, compared with standard care, for patients enrolled in the phase III ENHANCE-2 trial. (aacrjournals.org)
  • the company also just ended codevelopment of I-Mab's lemzoparlimab, another CD47 inhibitor, besides recently dropping Harpoon Therapeutics' anti-BCMA trispecific T-cell engager, HPN217. (aacrjournals.org)
  • Induction of stemness in TNBC sensitized cells to PYK2 and PKCα inhibition suggesting that targeting the AXL-PYK2-PKCα circuit could be an efficient strategy to eliminate CSCs in TNBC. (life-science-alliance.org)
  • Selective inhibition of EGFR downstream signaling reverses the irradiation-enhanced migration of HNSCC cells. (ajcr.us)
  • CD47 is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells. (wikipedia.org)
  • Compared with normal cells, tumor cells secrete more exosomes, and the number of exosomes secreted by different tumor cells varies dramatically [ 6 ]. (hindawi.com)
  • To realize the full potential of anti-CD47 therapy for both hematologic and solid malignancies, the SAFEbody technology enables IgG1-mediated strong effector functions for potent tumor killing, while minimizing antigen sink and red blood cell (RBC) depletion with an approximately 8-fold prolonged half-life for convenient drug dosing and administration. (adagene.com)
  • Endogenous biomolecules (such as lactate dehydrogenase) or previously added exogenous labels (such as the radioisotope 51Cr) that leak into the media are then measured as an indirect readout of the damage caused by effector cells. (technologynetworks.com)
  • Wu and colleagues identify gene networks and transcription factors that control the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8 + CAR T cells. (nature.com)
  • Celgene acquired EngMab for $600MM to enrich its programs targeting B-cell maturation antigen (BCMA) for the treatment of multiple myeloma. (shu.edu)
  • FT536 carries a CAR targeting the pan-tumor associated antigens MICA and MICB (MICA/B) and the product can be consistently and uniformly produced as well as cryopreserved at clinical scale. (sitcancer.org)
  • Multi-targeting through the CAR and CD16-mediated ADCC was also demonstrated when FT536 was combined with trastuzumab or cetuximab for HER2- or EGFR-expressing tumors, respectively. (sitcancer.org)
  • Thus, dual-targeting body allow for efficacious yet safe targeting of CD47 in malignancy. (ece-inhibitor.com)
  • Dual targeting FP T cells were also generated through the incorporation of scFvs into other CD3 subunits and CD28. (cartherics.com)
  • Bantug and Hess discuss the metabolic interplay between tumor-resident cells and how the effect of metabolism-targeted anticancer strategies on non-transformed or immune cells in the tumor needs to be considered. (nature.com)
  • Accordingly, modifying the structure of CAR T cells to attenuate the inhibitory effect of TME thus reducing recurrence rate is a valuable research topic. (bvsalud.org)
  • Strategies to repolarize TAMs, deplete TAMs, and block inhibitory signaling hold great potential in tumor therapy. (springer.com)
  • Importantly, EMT and BC initiating cells display very similar gene signatures and phenotypic properties ( 9 , 10 ). (life-science-alliance.org)
  • There is now considerable evidence, derived mainly from immunohistochemical and gene expression studies, suggesting that tumors enriched in EMT markers are associated with an immunosuppressive TME and a negative prognosis. (encyclopedia.pub)
  • PAQR3: a novel tumor suppressor gene. (ajcr.us)
  • Three-dimensional assessment of bystander effects of mesenchymal stem cells carrying a cytosine deaminase gene on glioma cells. (ajcr.us)
  • These cells displayed FP integration within the TCR/CD3 complex, lower variability in gene expression compared to CAR-T cells and good cell expansion after transfection. (cartherics.com)
  • In particular, we are very excited about our highly differentiated anti-CD47 SAFEbody in IgG1 format, which introduces IgG1-mediated effects for potent tumor killing with a compelling safety profile and 8-fold prolonged half-life. (adagene.com)
  • Potent and persistent antigen-specific cytotoxicty was demonstrated against an array of solid and hematological tumor lines. (sitcancer.org)
  • CD47 ligation leads to cell death in many normal and tumor cell lines via apoptosis or autophagy. (wikipedia.org)
  • The activation of CD47 induces rapid apoptosis of T cells. (wikipedia.org)
  • The apoptosis inducing function of CD47 appears to be dependent on activation of specific epitopes on the extracellular domain. (wikipedia.org)
  • Similarly, CD47 ligation rapidly induces apoptosis in B-cell chronic lymphocytic leukemia (CLL) cells. (wikipedia.org)
  • Induction of autophagy and apoptosis by miR-148a through the sonic hedgehog signaling pathway in hepatic stellate cells. (ajcr.us)
  • This cross-talk between EMT tumor cells and immune cells can occur both between EMT tumor cells and cells of either the native or adaptive immune system. (encyclopedia.pub)
  • Two of the proteins (ROR2 and CD47) involved in this study are expressed on the surface of LMS cells. (sarcomahelp.org)
  • Regardless of the type or the physiological or pathological state of the originating cell, exosomes share common features as enriched with nucleic acids, lipids, and proteins [ 4 ]. (hindawi.com)
  • We optimized the method of nonviral, CRISPR/Cas9 genome editing using large donor DNA delivery, knocked-in an anti-tumor single chain variable fragment (scFv) into the N-terminus of CD3ε and efficiently generated fusion protein (FP) T cells. (cartherics.com)
  • Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. (lu.se)
  • There are several upcoming projects in Dr. Terabe's lab investigating the role of NKT cells specifically in glioblastoma, which is an area that has not been previously well investigated. (cancer.gov)
  • Loss of CD47 allows sustained proliferation of primary murine endothelial cells and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. (wikipedia.org)
  • Expression of several stem cell markers, including c-Myc, is elevated in CD47-null endothelial cells and a human T cell line lacking CD47. (wikipedia.org)
  • Activation of CD47 with TSP-1 in wild-type cells inhibits proliferation and reduces expression of stem cell transcription factors. (wikipedia.org)
  • Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). (nih.gov)
  • Numerous studies have highlighted the role of different signaling pathways and signaling intermediates in regulating BC stem cells (BCSCs) self-renewal and maintenance of stemness properties, including the TGFβ, IL6/IL8, Hedgehog, Notch, Wnt, AXL, and the Hippo pathways ( 6 ). (life-science-alliance.org)
  • Dual-Fluorescence Viability, using acridine orange (AO) and propidium iodide (PI), is the recommended method for accurate viability analysis of primary cells, such as PBMCs, splenocytes, and stem cells in samples containing debris and unwanted non-nucleated cell types, such as red blood cells. (netlify.app)
  • Cell Stem Cell. (ucsf.edu)
  • Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques. (ucsf.edu)
  • Author Correction: Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. (ucsf.edu)
  • Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice. (ucsf.edu)
  • Kroeze KL, Jurgens WJ, Doulabi BZ, van Milligen FJ, Scheper RJ, Gibbs S: Chemokine-mediated migration of skin-derived stem cells: predominant role for CCL5/RANTES. (exbio.cz)
  • These preclinical findings support further development of FT536 as a universal adoptive cell therapy. (sitcancer.org)
  • Dr. Matt van de Rijn explains the difficulty of treating LMS: 'The challenge that leiomyosarcoma poses for the treating physician is that surgery remains the major avenue of therapy for this tumor. (sarcomahelp.org)
  • Targeted' therapy starts with the discovery of a protein that is expressed on the surface of tumor cells but not (or in a limited way) in normal human tissues. (sarcomahelp.org)
  • An example of such a targeted therapy can be found in GIST, where the KIT protein is expressed on almost all GIST tumors and where this protein can be inhibited by Gleevec. (sarcomahelp.org)
  • While CAR-T cell therapy has had remarkable success against most types of blood cancers, its application to T cell cancers is limited. (cartherics.com)
  • However, since both the malignant T cell and the therapy may share the target, CAR-T cells could kill healthy cells in the patient. (cartherics.com)
  • The long non-coding RNA lnc-ZNF180-2 is a prognostic biomarker in patients with clear cell renal cell carcinoma. (ajcr.us)
  • Its presence in the extracellular matrix is induced by injuries that cause thrombospondin-1 release from platelets and conditions including hyperglycemia, ischemia, and aging that stimulate its expression by many cell types. (bvsalud.org)
  • A total of 318 differentially expressed genes were associated with anti-CD47 treatment, with enrichment for reduced signatures of extracellular matrix remodeling and upregluation of pathways involved in tertiary lymphoid structure formation. (sitcancer.org)