• To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. (nature.com)
  • In this respect, the introduction of checkpoint inhibitors to unleash the activity of tumor-reactive T cells has been a milestone in cancer immunotherapy. (nature.com)
  • Adoptive cell transfer (ACT) is a promising form of cancer immunotherapy, which involves the isolation and reinfusion of tumour specific T lymphocytes into patients. (edu.au)
  • Nevertheless, ex vivo activation with cytokines can restore cytolytic activity of NK cells against GB, indicating that NK cells have potential for adoptive immunotherapy of GB if potent cytotoxicity can be maintained in vivo . (frontiersin.org)
  • NK cells play a pivotal role in rapid and highly efficient cancer surveillance and represent a promising avenue for adoptive cell transfer either as a mono- or combination immunotherapy. (maxcyte.com)
  • T cell-based immunotherapy, such as immune checkpoint blockade or adoptive T cell transfer, is limited by the ability of T cells to detect major histocompatibility complex (MHC)-presented antigen by tumor cells. (elifesciences.org)
  • Although murine CTL generated in vitro in response to IL-12 or IFN-α had comparable effector functions, IL-12-stimulated cells were significantly more effective in controlling tumor in an adoptive immunotherapy model. (aai.org)
  • Adoptive immunotherapy using tumor-associated antigen (TAA)-specific CD8 + cytotoxic T lymphocytes (CTLs) and/or CD4 + helper T (Th) cells can induce the regression of large established tumor in not only mouse models but also cancer patients [ 1 - 3 ]. (oncotarget.com)
  • These preclinical and clinical evidences encourage us to develop T-cell adoptive immunotherapy using genetically engineered T cells that are transduced with a T-cell receptor (TCR) gene specific for TAA. (oncotarget.com)
  • In vivo, i.v. transferred Tc1 trafficked efficiently into i.c. (nih.gov)
  • We found that tumor-intrinsic LRFN2 inhibited the recruitment and functional transition of CD8+ T cells by reducing the secretion of pro-inflammatory cytokines and chemokines, and this mechanism was verified in vitro and in vivo. (bvsalud.org)
  • We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model. (biomedcentral.com)
  • Proliferative/expansion potential, phenotypical characteristics and functionality of the propagated CD19CAR T cells were analyzed in vitro and in vivo after 17-21 day ex vivo expansion. (biomedcentral.com)
  • Inhibition of Akt signaling during ex vivo priming and expansion gives rise to CD19CAR T cell populations that display comparatively higher antitumor activity. (biomedcentral.com)
  • Manufacturing CAR T cells is a process that involves activation and ex vivo culture with IL-2 to facilitate CAR gene transfer and to achieve a therapeutic number of T cells. (biomedcentral.com)
  • The transferred, expanded natural killer cells proliferated in vivo in an interleukin-2 dose-dependent fashion, persisted up to 4 weeks, were readily detectable in the human bone, inhibited myeloma growth and protected bone from myeloma-induced osteolysis. (haematologica.org)
  • However, to our knowledge, the use of agonistic antibodies to CD40 to boost adoptively transferred T cells in vivo has not been investigated. (elsevierpure.com)
  • When administrated in vivo, both intact and Fab of J43 are reported to enhance contact hypersensitivity and exacerbate acute GVHD similar to transfer of PD-1-deficient cells. (thermofisher.com)
  • To this end, Dr. Rosenberg and others developed a "Young TIL" approach that rapidly expands TIL for administration without in vitro selection for tumor reactivity [ 8 ], which markedly improves the timeliness of TIL production as well as its survival and efficacy in vivo (Fig. 1 ). (biomedcentral.com)
  • In vitro observations were translated using an in vivo xenograft NSG mouse model of human cervical carcinoma evaluating cisplatin in combination with CTL adoptive cell transfer. (bmj.com)
  • The concept of enhancing cellular immunity through the transfer of ex-vivo expanded T cells was pioneered by Greenberg et al. (biomedcentral.com)
  • Here, we describe the pre-clinical in vitro and in vivo study of irradiated haNK cells engineered to express a second-generation chimeric antigen receptor (CAR) targeting programmed death-ligand 1 (PD-L1). (elifesciences.org)
  • Although the efficacy of adoptive transfer of tumor infiltrating lymphocytes (TILs) was examined over several decades, genetically engineered T cells expressing chimeric antigen receptors (CARs) rapidly replaced the application of TILs due to their high specificity, non-MHC-restricted recognition of tumor antigen, superior potency, and improved in vivo persistency [ 9 , 13 , 14 ]. (biomedcentral.com)
  • Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. (biomedcentral.com)
  • There remains an urgent need for the noninvasive tracking of transfused chimeric antigen receptor (CAR) T cells to determine their biodistribution, viability, expansion, and antitumor functionality. (snmjournals.org)
  • Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. (hindawi.com)
  • Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. (ashpublications.org)
  • Moreover, γδ T cells can directly kill target cells without the involvement of dendritic cells (DCs) and perform dual functional roles in antitumor and anti-infective immunity. (nature.com)
  • LRFN2 restrained antitumor immunity by inhibiting the infiltration, proliferation, and differentiation of CD8+ T cells in vitro. (bvsalud.org)
  • To determine the mechanisms of how innate immune activation via lymphodepletion potentiated antitumor T cell immunity, we utilized the pmel-1 melanoma mouse model. (biomedcentral.com)
  • Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity. (biomedcentral.com)
  • Combination with cyclophosphamide further induces ICD, depletes Treg, and thus potentiates antitumor immunity. (biomedcentral.com)
  • The antitumor immunity helps eliminate the uninfected cancer cells in primary and metastatic nodules, and enforce micrometastases in dormant state. (biomedcentral.com)
  • Functional assays performed in vitro indicated that murine CARaMEL T cells mediated antigen-specific cytokine secretion and killing abilities against pancreatic cancer cells, and demonstrated potent proliferative ability in response to gp100 antigen, confirming our hypothesis. (edu.au)
  • In vitro functional assays indicated that human CARaMEL T cells mediated powerful and antigen-specific killing and cytokine secretion against Her2, together with a strong proliferative ability in response to gp100 antigen. (edu.au)
  • 1] Early methods to generate many tumor-reactive T cells for adoptive transfer to tumor individuals involved repetitive in vitro excitement with antigen, had been cumbersome, and met with clinical achievement infrequently. (cancer-ecosystem.com)
  • Adoptive T-cell therapy with T cells expressing chimeric antigen receptors (CARs) is an active area of cancer research. (ashpublications.org)
  • 12 , 13 Clinical trials in which patients with advanced B-cell malignancies receive T cells expressing anti-CD19 CARs are in early stages, and it is not known whether adoptive transfer of T cells targeting this self-antigen will be an effective therapy for B-cell malignancies. (ashpublications.org)
  • Using C57BL/6 mice bearing intracranial (i.c.) ovalbumin-transfected melanoma (M05), we evaluated the efficacy and tumor homing of i.v. transferred type 1 or 2 CTLs (Tc1 or Tc2, respectively) prepared from ovalbumin-specific T-cell receptor-transgenic OT-1 mice. (nih.gov)
  • Anti-tumor activity was evaluated after adoptive transfer of the CD19CAR T cells into CD19+ tumor-bearing immunodeficient mice. (biomedcentral.com)
  • Once adoptively transferred into CD19+ tumor-bearing mice, Akti treated CD19CAR T cells exhibited more antitumor activity than did untreated CD19CAR T cells. (biomedcentral.com)
  • These mice are devoid of endogenous natural killer and T-cell activity and were used to determine whether adoptively transferred expanded natural killer cells could inhibit myeloma growth and myeloma-associated bone destruction. (haematologica.org)
  • In addition, I found that the administration of both human CARaMEL T cells and an adenovirus vaccine expressing gp100 led to potent anti-tumour activity against subcutaneous human Her2+ pancreatic tumours in immunodeficient mice. (edu.au)
  • B16F10-bearing mice were preconditioned with 5Gy TBI and given a tripartite ACT therapy (consisting of transferred pmel-1 CD8 + T cells, vaccination with fowlpox encoding gp100, and IL-2) along with TLR4 agonist LPS. (biomedcentral.com)
  • We analyzed both the phenotype and activity of neutrophils isolated from the spleens of TCL1 leukemia-bearing mice. (biomedcentral.com)
  • To investigate the interrelation between Treg and neutrophils in the leukemia microenvironment, we performed experiments using TCL1-injected DEREG mice with Treg depletion or RAG2KO mice with adoptively transferred TCL1 cells alone or together with Treg. (biomedcentral.com)
  • However, studies have shown that the sustained activity of Akt progressively drives T cells toward terminal differentiation and diminished anti-tumor activity [ 11 ]. (biomedcentral.com)
  • One mechanism of NK cell anti-tumor activity is antibody-dependent cellular cytotoxicity (ADCC) induced via Fc receptor (CD16) binding to antibodies. (maxcyte.com)
  • Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. (biomedcentral.com)
  • The purpose of this study was to determine whether anti-CD40 monoclonal antibody (mAb) in combination with interleukin (IL)-2 could improve the efficacy of in vitro-activated T cells to enhance antitumor activity. (elsevierpure.com)
  • Current methods used to predict or monitor the activity of infused T cells in patients provide limited data on treatment efficacy ( 6 , 7 ). (snmjournals.org)
  • Early studies on the transfer of unmodified autologous or allogeneic NK cells have established their clinical safety and demonstrated modest anti-tumor efficacy. (maxcyte.com)
  • Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 reg-imens enhances efficacy in a synergistic manner. (unav.edu)
  • Adoptive transfer of expanded natural killer cells inhibited the growth of established OPM2 and high-risk primary myeloma tumors grown in the murine model. (haematologica.org)
  • Since regulatory T cells (Treg) play an important role in CLL progression and influence the activity of neutrophils, we investigated the crosstalk between Treg and neutrophils in the spleen using a murine model of CLL. (biomedcentral.com)
  • To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. (ashpublications.org)
  • Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19-CAR-transduced T cells in a clinically relevant murine model. (ashpublications.org)
  • To establish a murine model in which a completely syngeneic lymphoma could be treated by adoptive transfer of syngeneic CAR-transduced T cells, we developed a CAR that could specifically recognize murine CD19. (ashpublications.org)
  • These data suggest that Tc1-based adoptive transfer therapy may represent an effective modality for CNS tumors, particularly when combined with strategies that promote a type 1 polarized tumor microenvironment. (nih.gov)
  • Local administration or OV mediated-expression of ligands for Toll-like receptors can rescue the function of tumor-infiltrating CD8 + T cells inhibited by the immunosuppressive tumor microenvironment and thus enhances the antitumor effect. (biomedcentral.com)
  • ANDERSON, A K, STROMNES I M, GREENBERG P D. Obstacles posed by the tumor microenvironment to T cell activity: a case for synergistic therapies[J]. Cancer Cell , 2017 , 31 (3): 311-325. (cip.com.cn)
  • Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to treat patients. (biomedcentral.com)
  • Its diverse TCR clonality, superior tumor-homing ability, and low off-target toxicity endow TIL therapy unique advantages in treating solid tumors compared with other adoptive cellular therapies. (biomedcentral.com)
  • TIL therapy is a type of adoptive cellular therapy leveraging the patient's own immune system to treat tumors. (biomedcentral.com)
  • We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. (nature.com)
  • Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into effector T cell states. (bvsalud.org)
  • Thus, the mechanism of action of Ipilimumab has been presumed to involve releasing anti-tumor effector T cells from CTLA-4-inhibition and/or limiting T REG activity in the tumor and therefore resulting in an increase in the ratio of effector T cells/ T REG s within the tumor. (sanguinebio.com)
  • Even though GITR-activation in effector T cells promotes activities including cytokine production and proliferation, the agonistic properties of this antibody alone were not effective in the absence of activating FcgR engagement. (sanguinebio.com)
  • This review will discuss the metabolic changes that drive T cells into different stages of their development and how the TME imposes barriers to the metabolism and activity of tumor infiltrating lymphocytes. (elifesciences.org)
  • Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on antig en-presenting cells (APC). (thermofisher.com)
  • Currently, the most widely-used TIL production method is to isolate infiltrating lymphocytes from tumor tissues and then culture and expand these cells in vitro. (biomedcentral.com)
  • Therefore, I directed my study to augment the anti-tumour activity of ACTIV therapy by the administration of either a histone deacetylase inhibitor (Panobinostat) or an immune agonist monoclonal antibody specific for CD40. (edu.au)
  • Antitumor effects of agonist anti-CD137 mAbs are critically dependent on the integrity of cIAPs in cancer mouse models, and cIAPs are also required for signaling from CARs encompassing CD137's cytoplasmic tail. (unav.edu)
  • While increased CD16 expression was transient in nature, this may not negatively impact the therapeutic potential of engineered NK cells due to the short persistence of adoptively transferred NK cells. (maxcyte.com)
  • After leukapheresis even though CAR-T cells are becoming Homotaurine manufactured, patients generally in most protocols will receive lymphodepleting chemotherapy, which creates a good immune system environment for moved CAR-T cells adoptively, improving their enlargement, following persistence, and medical activity (Fig 2). (cancer-ecosystem.com)
  • Specifically, demonstrate efficient expression of high-affinity CD16 in NK cells with minimal effects on cell viability and phenotype using mRNA electroporation and assess the effects of CD16-158V expression on rituximab - mediated cytotoxic activity against B cell lymphoma cells. (maxcyte.com)
  • In vitro cytotoxic activity against rituximab-coated CD20+ B cell lymphoma cells of CD16-engineered or non-engineered NK cells was assessed 24 hours post electroporation. (maxcyte.com)
  • In vitro , CD3 + CD8 + CD27 - CD28 - compared to CD3 + CD8 + CD27 + CD28 + CART cells displayed similar CD19 + target cell-specific cytotoxicity, but were hypoproliferative and produced less cytotoxic cytokines (IFN-γ and TNF-α). (frontiersin.org)
  • We hypothesized that adoptively transferred CARaMEL T cells would proliferate mediated by their gp100 TCR, in response to the VV-gp100 vaccine, and kill Her2+ tumours through their anti-Her2 CAR. (edu.au)
  • Thus, when cultured alone without special treatment, CLL cells do not proliferate under in vitro conditions. (biomedcentral.com)
  • We also tested our hypothesis that intratumoral (i.t.) delivery of dendritic cells that had been transduced with IFN-alpha cDNA (DC-IFN-alpha) would enhance the tumor-homing and antitumor effectiveness of adoptively transferred Tc1 via induction of an IFN-gamma-inducible protein 10 (IP-10). (nih.gov)
  • NK cells contribute to cancer immune surveillance not only by their direct natural cytotoxicity which is triggered rapidly upon stimulation through germline-encoded cell surface receptors, but also by modulating T-cell mediated antitumor immune responses through maintaining the quality of dendritic cells and enhancing the presentation of tumor antigens. (frontiersin.org)
  • Results We showed that subpopulations surviving clinically relevant doses of radiation or cisplatin therapy were more susceptible to CTL-mediated lysis in four of four tumor models of HPV-associated malignancies, serving as a model for HPV therapeutic vaccine or T-cell receptor adoptive cell transfer. (bmj.com)
  • Two of the primary immunotherapies are immune checkpoint blockade (ICB) and adoptive cell transfer (ACT). (elifesciences.org)
  • Lymphodepletion enhances adoptive T cell transfer (ACT) therapy by activating the innate immune system via microbes released from the radiation-injured gut. (biomedcentral.com)
  • In contrast, administering LPS after ACT potentiated the antitumor effectiveness of the regimen, thereby supporting the expansion of transferred tumor-specific CD8 + T cells over host CD4 + T cells. (biomedcentral.com)
  • We tested whether natural killer cells expanded by co-culture with K562 cells transfected with 41BBL and membrane-bound interleukin-15 could kill myeloma cells with a high-risk gene expression profile in vitro and in a unique model which recapitulates human myeloma. (haematologica.org)
  • We found that Akt inhibition did not compromise CD19CAR T cell proliferation and expansion in vitro, independent of the T cell subsets, as comparable CD19CAR T cell expansion was observed after culturing in the presence or absence of Akt inhibitor. (biomedcentral.com)
  • In this model, the combination of anti-CD40 mAb with IL-2 led to expansion of adoptively transferred T cells and induced a more robust antitumor response. (elsevierpure.com)
  • The use of neutralizing mAb to IL-12 provided direct evidence that enhanced IL-12 secretion induced by anti-CD40 mAb was crucial for the expansion of adoptively transferred T cells. (elsevierpure.com)
  • Panobinostat significantly suppressed the growth of pancreatic cancer cells in vitro through apoptosis and cell cycle arrest. (edu.au)
  • Here we report that while exogenous administration of LPS was able to enhance adoptively transferred CD8 + T cells' tumor destruction, LPS treatment alone did not replace individual components of the tripartite ACT regimen, or obviate TBI. (biomedcentral.com)
  • Only 10% of the human population is homozygous for this polymorphism, suggesting that genetic manipulation of NK cells to express CD16-158V prior to adoptive transfer may improve clinical success not only of NK cell therapies but also anti-tumor IgG1 antibodies. (maxcyte.com)
  • Collectively, these findings provide a rationale to evaluate the potential application of anti-CD40 mAb in adoptive T-cell therapy for cancer. (elsevierpure.com)
  • Non-viral engineering of NK cells using MaxCyte ® mRNA electroporation provides significant benefits including high efficiency and low toxicity as well as clinical scalability enabling rapid development of novel adoptive cell therapy approaches. (maxcyte.com)
  • Establish overexpression of high-affinity CD16 on NK cells as a potential combination therapy for improving ADCC activity of anti-tumor monoclonal antibodies. (maxcyte.com)
  • Adoptive T-cell therapy with T cell receptor (TCR) -engineered T cells is an attractive strategy for cancer treatment and the success in this therapy is dependent on the functional avidity of the transduced TCRs against targeted tumor antigens. (oncotarget.com)
  • M05 and mediated antitumor responses more effectively than Tc2, and their effect was IP-10 dependent. (nih.gov)
  • In vitro, DC-IFN-alpha induced IP-10 production by M05 and enhanced the cytolytic activity of Tc1. (nih.gov)
  • CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models, and multiple agents of this kind are undergoing clinical trials. (unav.edu)
  • The anticancer activities of OVs are derived from multimodal cancer killing mechanisms. (biomedcentral.com)
  • To examine endothelial dysfunction in SSc patients and to correlate findings with biochemical markers of endothelial injury, circulating EPC count, disease activity and organ involvement. (hku.hk)
  • We develop a multifocal HCC model to test immunotherapies by introducing c-myc using hydrodynamic gene transfer along with CRISPR-Cas9-mediated disruption of p53 in mouse hepatocytes. (unav.edu)