Cells receptors antigen t cell. Medical search. Frequent questions

Chimeric antigen receptor-modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). (nih.gov)
Two children with relapsed and refractory pre-B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×10(6) to 1.2×10(7) CTL019 cells per kilogram of body weight. (nih.gov)
The other patient had a relapse, with blast cells that no longer expressed CD19, approximately 2 months after treatment. (nih.gov)
The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL. (nih.gov)
it recognizes a specific protein on the surface of malignant cells (eg, CD19 on B-cells). (medscape.com)
Kochenderfer et al described dramatic regression of the lymphoma after infusion of CAR T cells engineered to target CD19. (medscape.com)
We designed a lentiviral vector expressing a chimeric antigen receptor with specificity for the B-cell antigen CD19, coupled with CD137 (a costimulatory receptor in T cells [4-1BB]) and CD3-zeta (a signal-transduction component of the T-cell antigen receptor) signaling domains. (nih.gov)
A specific immune response was detected in the bone marrow, accompanied by loss of normal B cells and leukemia cells that express CD19. (nih.gov)
Of note, CD19, CD20, CD30, CD33, CD123, and CD269 as ideal targets have shown extraordinary potential for CAR-T cell therapy and other targets such as CD23 and SLAMF7 have brought promising future for clinical trials. (hindawi.com)
One example is adoptive cell therapy with T cells that were genetically modified with gamma-retroviral and lentiviral (LV) delivery vectors to express a CD19-specific chimeric The advances in genetic engineering have enabled us to confer T cells new desired functions or delete their specific undesired endogenous properties for improving their antitumor function. (uni-wuerzburg.de)
One example is adoptive cell therapy with T cells that were genetically modified with gamma-retroviral and lentiviral (LV) delivery vectors to express a CD19-specific chimeric antigen receptor (CAR) for cancer treatment. (uni-wuerzburg.de)
Importantly, CD19-CAR T cells modified by MC-based SB transposition were equally effective as LV transduced CD19-CAR T cells in vitro and in a murine xenograft model (NSG/Raji-ffLuc), where a single administration of CD8+ and CD4+ CAR T cells led to complete eradication of lymphoma and memory formation of CAR T cells after lymphoma clearance. (uni-wuerzburg.de)
In this study, the well characterized CD19-specific 2nd generation CAR, signaling through CD28 and CD3-ζ endodomains, was expressed in donor T cells. (bmj.com)
The aAPC were genetically modified to present the target antigen CD19 along with no co-stimulation, or co-stimulation via CD86, CD137L, or both molecules. (bmj.com)
Several antigens have been used as targets for CAR-T cell therapy against MM, including B cell maturation antigen (BCMA), CD19, CD138, signaling lymphocytic activation molecule 7 (SLAM7), and immunoglobulin light chains. (biomedcentral.com)
Fig. 1: CAR19-mediated trogocytosis in NK cells cocultured with CD19 + tumor targets. (nature.com)

One way to achieve this is to genetically modify immune cells, mainly T cells and recently also natural killer (NK) cells, to express chimeric antigen receptors (CARs). (nature.com)
The therapy they have developed primarily involves the modification of a patient's own T cells to express chimeric antigen receptors, allowing them to recognize and attack cancer cells. (bestcollegetutors.com)

Chimeric antigen receptor-modified T cells are capable of killing even aggressive, treatment-refractory acute leukemia cells in vivo. (nih.gov)
A low dose (approximately 1.5×10(5) cells per kilogram of body weight) of autologous chimeric antigen receptor-modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia (CLL) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission. (nih.gov)

These receptors have both extracellular and intracellular components. (medscape.com)
Extracellular matrix receptor and platelet antigens on osteoclasts and foreign body giant cells. (ox.ac.uk)
Osteoclasts (OCs) and other cells of the mononuclear phagocyte system possess receptors for adhesive proteins present in the extracellular matrix. (ox.ac.uk)
Chimeric antigen receptor (CAR) T cell therapy has emerged as a novel immunotherapy which modifies T cells with CAR, an artificial fusion protein that incorporates an extracellular antigen recognition domain, a transmembrane domain, and an intracellular domain including costimulation and signaling components [ 4 , 5 ]. (biomedcentral.com)
Classical " CARs consist of an extracellular binding domain mostly derived from a monoclonal antibody fragment (single-chain variable fragment-scFv), which is linked to intracellular binding domains of the T-cell receptor complex. (nature.com)
Once these stores are depleted the ER-bound calcium sensor Stim1 (Stromal interaction molecule 1) couples the ER to the cytosolic Ca2+ channel protein Orai1 allowing extracellular calcium to enter the cell via store-operated calcium mineral admittance (SOCE) (evaluated in Feske 2007 Hogan et al. (ecologicalsgardens.com)

These insights into the nature of TCR assembly and the unusual cell membrane architecture reveal the basis of antigen recognition and receptor signaling. (nanotech-now.com)
Natural killer (NK) cell-based immunotherapy may overcome genetic mechanisms of resistance to T cell-based immunotherapy through antigen- and MHC-independent recognition of malignant cells. (elifesciences.org)
Results: In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon gamma, interleukin 2 and tumour necrosis factor a. (uninsubria.it)
CAR-expression on T or NK cells allows them to specifically target cancer cells via recognition of tumor associated antigens. (nature.com)
Furthermore, the so-called adapter CARs have been developed by splitting antigen recognition and CAR-immune cell activation. (nature.com)
Furthermore, similar to T cells, specific recognition and elimination of cancer cells by NK cells can be markedly enhanced through expression of chimeric antigen receptors (CARs), which provides an opportunity to generate NK-cell therapeutics of defined specificity for cancer immunotherapy. (frontiersin.org)
CDR2s interact with the class II molecules but are not involved in antigen recognition. (pharmacygyan.com)
CDR4 of the β-chain is not thought to participate in antigen recognition, but has been shown to interact with superantigens. (wikipedia.org)
recognition of the target tumor-associated antigen, followed by CAR T cell activation, expansion, and immune-killing of the cancer cells, as well as sufficient persistence to provide immune surveillance for tumor control. (apbmt.org)
Recent years have seen the emergence of many strategies to spatiotemporally control CAR-T cell activities through regulating antigen recognition [ 5 , 6 ], but the application of tumor environmental signals (e.g., acidosis and hypoxia) may represent an attractive strategy to control CAR-T cells. (biomedcentral.com)
We aimed to develop a CAR design that require both antigen recognition and hypoxia sensing to generate optimal T cell activity, thereby reducing on-target off-tumor toxicity. (biomedcentral.com)

For the structural analysis, the researchers chose a T-cell receptor used in immunotherapy to treat melanoma and which had been optimized for this purpose in several steps in such a way that it binds its antigen as tightly as possible. (news-medical.net)
Novel understanding in the interaction between immune system and cancer cells of the patient holds great promise for immunotherapy development [ 4 - 6 ]. (hindawi.com)
It is noted that T cell has great potential for immunotherapy of hematological malignancies. (hindawi.com)
Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. (elifesciences.org)
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)
Thus, addressing the presence of immunosuppressive myeloid cell populations in the periphery and tumor microenvironment of patients with cancer is likely to be required for effective NK cell-based immunotherapy. (elifesciences.org)
Immunotherapy utilizing T cell immunity has become a new treatment to eliminate cancer cells. (biomedcentral.com)
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)
We then outline preclinical approaches that employ CAR-NK cells for GB immunotherapy, and give an overview on the ongoing clinical development of ErbB2 (HER2)-specific CAR-NK cells currently applied in a phase I clinical trial in glioblastoma patients. (frontiersin.org)
Fig. 4: A lower level of CAR-mediated TROG-antigen expression was associated with improved clinical response to CAR-NK cell-based immunotherapy. (nature.com)
Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. (oncotarget.com)
These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen. (oncotarget.com)
Chimeric antigen receptor ( CAR ) T cells , the breakthrough in cancer immunotherapy , have revolutionized the treatment of B cell malignancies and remarkably improved the prognosis of RRMM. (bvsalud.org)
Overall, our study demonstrates the potential of the HiCAR for improving the safety of CAR-T cells to promote the clinical application of CAR-T immunotherapy. (biomedcentral.com)

Many surface receptors relay signals into the interior of the cell by changing their spatial structure after ligand binding. (news-medical.net)
The most active T cell endogenous inhibitory pathway is the immunoglobulin superfamily such as CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4): B7-1/B7-2 receptor/ligand grouping, which plays a central role in coordinating immune responses [ 7 , 8 ]. (hindawi.com)
The cryo-EM structure of the fully assembled T-cell receptor (TCR) complex with a tumor-associated peptide/MHC ligand provides important insights into the biology of TCR signaling. (nanotech-now.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)
It is closely associated with B cell-activating factor of the TNF family (BAFF) receptor, transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) [ 14 ]. (biomedcentral.com)
To test this hypothesis, both an Ag‐specific mouse B cell clone CH12.LX, and freshly isolated resting splenic B cells were cultured with either soluble or membrane‐bound forms of the T cell ligand for CD40 (CD40L), in the presence or absence of additional signals provided by Ag or anti‐IgM, interleukin‐4, and class II‐specific monoclonal antibody (mAb). (uthscsa.edu)
Bishop, GA, Warren, WD & Berton, MT 1995, ' Signaling via major histocompatibility complex class II molecules and antigen receptors enhances the B cell response to gp39/CD40 ligand ', European Journal of Immunology , vol. 25, no. 5, pp. 1230-1238. (uthscsa.edu)

Ad-mTNFa-mIL2 increased both CAR T cell and host T cell infiltration to the tumor and altered host tumor immune status with M1 polarization of macrophages and increased dendritic cell maturation. (jci.org)
Moreover, BCMA plays an essential role in regulating B cell maturation and differentiation into plasma cells. (biomedcentral.com)
Immunotherapies are changing the treatment paradigm of MM and have improved the overall response and survival of patients with relapsed/refractory (RR) MM. B cell maturation antigen (BCMA), selectively expressed in normal and malignant plasma cells , has been targeted by several immunotherapeutic modalities. (bvsalud.org)
Keywords: T-cell activation Chromatin decondensation Calcium NFAT 1 Intro Following maturation in the thymus peripheral T-cells enter into a quiescent state characterized by a low metabolic profile rudimentary organelles and extremely condensed chromatin. (ecologicalsgardens.com)

The subsequent images collected at the cryo-electron microscope delivered groundbreaking insights into how the T-cell receptor works, as Tampé summarises: 'On the basis of our structural analysis, we were able to show how the T-cell receptor assembles and recognizes antigens and hypothesize how signal transduction is triggered after antigen binding. (news-medical.net)
When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through signal transduction, that is, a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, and activated or released transcription factors. (wikipedia.org)

This includes exploring the use of inducible CAR-T cells and dual-targeted CAR-T cells to enhance specificity and reduce off-tumor effects. (bestcollegetutors.com)
The present study was designed to test the hypothesis that signals delivered via the B cell antigen (Ag) receptor (membrane immunoglobulin, mIg) and major histocompatibility complex (MHC) class II molecules enhance B cell responsiveness to CD40‐mediated signals, providing specificity to the Ag‐nonspecific, MHC‐unrestricted CD40 signal. (uthscsa.edu)

The first report of CAR T-cell therapy was in 2010, in a patient with advanced follicular lymphoma. (medscape.com)
In this review, we aim to summarize the composition of CAR-T cell and its application in the treatment of acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), multiple myeloma (MM), and acute myeloid leukemia (AML). (hindawi.com)
They can both be used to treat relapsed/refractory diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma. (pharmaceutical-journal.com)
In 1982, Nobel laureate James P. Allison first discovered a clonally expressed T-cell surface epitope in murine T lymphoma. (wikipedia.org)
The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) relies on chronic active B-cell receptor (BCR) signaling. (arizona.edu)
We speculated that binding of lymphoma BCRs to self-antigens initiates and maintains chronic active BCR signaling in ABC DLBCL. (arizona.edu)
Cutaneous T-cell lymphoma (CTCL) (see the image below) is a heterogeneous group of lymphoproliferative disorders characterized by localization of neoplastic T lymphocytes to the skin, with no evidence of extracutaneous disease at the time of diagnosis. (medscape.com)
Early patch-stage cutaneous T-cell lymphoma. (medscape.com)
Related articles include Cutaneous B-Cell Lymphoma and Cutaneous Pseudolymphoma . (medscape.com)
Among the changes to CTCL classification were the addition of primary cutaneous acral CD8 + T-cell lymphoma as a new provisional entity. (medscape.com)
Also, the term "primary cutaneous CD4 + small/medium T-cell lymphoma" was changed to "primary cutaneous CD4 + small/medium T-cell lymphoproliferative disorder" because of its indolent clinical behavior and uncertain malignant potential. (medscape.com)

Multiple myeloma (MM) is a hematological malignancy characterized by the proliferation of transformed monoclonal plasma cells in the bone marrow (BM) [ 1 ]. (biomedcentral.com)
Currently, autologous CAR T products are FDA-approved to treat B cell acute lymphoblastic leukemia (B-ALL), large B cell, mantle cell, and follicular lymphomas, and multiple myeloma. (hosct.org)

HLA, human leukocyte antigen. (cdc.gov)
Class II Human Leukocyte Antigen (HLA) play an important role in host protection from foreign. (hla-dr.com)
Background: Monocytic human leukocyte antigen DR (mHLA-DR) expression levels have been reported to be a marker of immunosuppression and predictors of sepsis and death. (hla-dr.com)

Here, we discuss effects of the GB tumor microenvironment on NK-cell functionality, summarize early treatment attempts with ex vivo activated NK cells, and describe relevant CAR target antigens validated with CAR-T cells. (frontiersin.org)
Chimeric antigen receptor (CAR) T cells are engineered T cells that are transduced to express an artificially modified receptor that directly binds to target antigens on tumor cells. (apbmt.org)

Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules. (uams.edu)
The antigenic phenotype of OCs and foreign body giant cells (FBGCs) was investigated for the presence of several integrin molecules and other largely platelet-associated antigens involved in cell adhesion reactions. (ox.ac.uk)
Both OCs and FBGCs expressed the alpha-chains of the vitronectin receptor (CD51) and of the VLA-2 (CDw49b) and VLA-4 (CDw49d) molecules as well as their respective beta-chains, gpIIIa (CD61) and CD29. (ox.ac.uk)
The addition of separate adapter molecules (AMs) specific for tumor antigens and CAR-immune cells targeting these AMs allows a more precise and temporally limited therapy. (nature.com)
Activation does not need antigen processing by APCs or presentation by MHC molecules. (pharmacygyan.com)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
As an evasion mechanism, many tumors are able to stimulate the expression of immune checkpoint molecules, resulting in an exhausted phenotype of T cells that cannot restrain tumor progression [ 1 ]. (oncotarget.com)
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. (wikipedia.org)
Activated T cells induce proliferation and differentiation of resting B cells in vitro through their CD40 molecules and lymphokine receptors. (uthscsa.edu)

The clonal selection theory, developed by MacFarland Burnet in the late 1950s, says that antigens, not cells, control the immune response. (pharmacygyan.com)
NK cells play an important role in the early immune response to cancer. (bgu.ac.il)
This T cell immune response in turn sets the stage for the toxicities that frequently accompany CAR T cell therapies, namely CRS and ICANS 1 . (apbmt.org)

In both patients, CTL019 T cells expanded to a level that was more than 1000 times as high as the initial engraftment level, and the cells were identified in bone marrow. (nih.gov)
The most up-to-date clinical data regarding UPenn's CAR-T cell therapy, known as CTL019, is highly encouraging. (bestcollegetutors.com)
In conclusion, the University of Pennsylvania's CAR-T cell therapy, CTL019, has shown promising results in the treatment of relapsed/refractory ALL. (bestcollegetutors.com)

CRS is a systemic inflammatory response caused by the activation and proliferation of T cells, resulting in fever, hypotension, capillary leak, and organ dysfunction. (bestcollegetutors.com)
Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. (bepress.com)
These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. (bepress.com)
Differentiation of CH12.LX cells and proliferation of splenic B cells in response to both forms of CD40L was greatly enhanced by exposure to mIg‐mediated signals, with greatest enhancement seen when cells were cultured with Ag prior to receiving other signals. (uthscsa.edu)
2000 In T-cells calcium mineral Ebastine signaling is necessary for activation proliferation and differentiation mainly through the experience of NFAT (Nuclear Element of Activated T-cells) a transcription element that becomes triggered because of improved intracellular calcium mineral ([Ca2+]we) (Macian 2005 It's been demonstrated that NFAT activation is essential for the manifestation of genes necessary for proper T-cell activation (evaluated in Hogan et al. (ecologicalsgardens.com)
2003 While TCR signaling regulates the activation of peripheral T-cells the next clonal proliferation necessary for a proper immune system response can be managed by Interleukin-2 (IL-2). (ecologicalsgardens.com)

3) The T cell's CD28 binds with a B7 molecule on the APC in the last stage of the activation cycle (antigen-presenting cell). (pharmacygyan.com)
The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while the Variable region binds to the peptide/MHC complex. (wikipedia.org)

Recently, chimeric antigen receptor (CAR) T cell therapy has transformed the treatment armamentarium of relapsed/refractory B lymphoid malignancies. (apbmt.org)
Tfh cells are mostly located in secondary lymphoid organs, e.g. (bvsalud.org)

Statistical comparison of all inhibitory and activating killer cell immunoglobulin receptors (KIRs) between controls, survivors, and persons who died of Ebola virus disease in Guinea, 2015-2017. (cdc.gov)
The MHC-TCR-CD3 interaction for T cells is functionally similar to the antigen(Ag)-immunoglobulin(Ig)-FcR interaction for myeloid leukocytes, and Ag-Ig-CD79 interaction for B cells. (wikipedia.org)
Polymorphisms in the capital Killer Cells Immunoglobulin-like Receptor (kirs). (hla-dr.com)

It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). (nih.gov)
Several types of adoptive cell transfer are under investigation, but CAR T-cell therapy is the first to enter clinical practice. (medscape.com)
Doctors, pharmacists and nurses are involved in providing clinical CAR-T cell therapy to patients. (pharmaceutical-journal.com)
Which of the following clinical trials was pivotal in gaining regulatory approval for CAR-T cells? (pharmaceutical-journal.com)
This therapeutic approach has shown remarkable results against B-cell malignancies in pilot clinical trials. (uni-wuerzburg.de)
Mesothelin-redirected chimeric antigen receptor T cell (meso-CAR T cell) therapy has shown some efficacy in clinical trials but antitumor efficacy remains modest. (jci.org)
The use of CAR+ T cells for the treatment of cancer is growing as multiple centers participate in Phase I/II clinical trials. (bmj.com)
To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. (uninsubria.it)
There is an unmet need to develop novel therapies for refractory/relapsed MM. In the past few years, chimeric antigen receptor (CAR)-modified T cell therapy for MM has shown promising efficacy in preclinical and clinical studies. (biomedcentral.com)
Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. (nature.com)
In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany. (nature.com)
Compose a brief, ~ 300-500 word report that explains the specific CAR-T cell approach being implemented and the most up-to-date clinical data you can find regarding the status of the therapy they have developed. (bestcollegetutors.com)
Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. (bepress.com)
This review focuses on BCMA-targeting CAR T cell therapy , covering all stages of investigational progress, including the innovative preclinical studies, the initial phase I clinical trials , and the more developed phase II clinical trials. (bvsalud.org)
Alternatively, allogeneic CAR T cell therapy, currently under clinical trial, has inherent disadvantages, including cell rejection, graft versus host disease, and undetermined safety and efficacy profiles. (hosct.org)

Engineered cells persisted at high levels for 6 months in the blood and bone marrow and continued to express the chimeric antigen receptor. (nih.gov)

The genetically modified autologous T cells are expanded in vitro at a production facility and then reinfused into the patient. (medscape.com)
An autologous CAR-T or NK cell therapy comprises several steps as shown in Fig. 1 . (nature.com)
Autologous chimeric antigen receptor (CAR)Tcell therapy has been extensively studied over the past decades. (hosct.org)

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)

In approved products, a patient's own T lymphocytes are collected by apheresis and transduced with a gene that encodes for a CAR to direct the T cells against cancer cells. (medscape.com)
OAd-TNFa-IL2 enhanced the antitumor efficacy of meso-CAR T cells in human-PDA-xenograft immunodeficient mice and efficacy was associated with robustly increased tumor-infiltrating lymphocytes (TILs), enhanced and prolonged T cell function. (jci.org)

Based on the promising results achieved from antibody-mediated PD-1 blockade in the treatment of hematological and solid tumors, we are confident that PD-1 knockout CAR T cells enhance the potency of CAR T cell therapies for treatment of cancers without the side effects of antibody-based therapies. (uni-wuerzburg.de)
Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. (nature.com)
Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. (nature.com)
BCMA-targeting CAR T cell therapy is the most developed CAR T cell therapy for MM, and the US Food and Drug Administration has already approved idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) for MM. However, the development of novel BCMA-targeting CAR T cell therapies remains in progress. (bvsalud.org)
What are CAR T cell therapy, RNA therapy, and other genetic therapies? (medlineplus.gov)

Removing senescent T cells from the physiological cycle to maintain the homeostasis of memory and effector T cells is the way of replacement. (hindawi.com)

Dennoch bestätigen funktionelle Assays eine höhere Avidität von Treg TCRs im Vergleich zu Nicht-Tregs TCRs gegenüber dem endogenen Selbst-Antigen MOG35-55. (tu-berlin.de)
To create a repertoire of antigen-specific TCRs, alternative forms of genes present in somatic cells are rearranged in a process, called somatic cell recombination, by using RAG-1 and RAG-2 recombinase activating enzymes showing in above figure. (pharmacygyan.com)
Simple recombination in the α-chain can result in approximately 4.9 × 103 antigen-specific TCRs. (pharmacygyan.com)
The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR. (wikipedia.org)

BCMA, a member of the tumor necrosis factor (TNF) superfamily, is exclusively expressed in a subpopulation of B cells, normal plasma cells, and malignant plasma cells. (biomedcentral.com)
BCMA is not present in other hematological cells like hematopoietic stem cells or other tissues. (biomedcentral.com)
Two main advantages of BCMA as an antigen for CAR-T therapy are the potential reduction of on-target/off-tumor toxicity and the lack of antigen-dependent reduction in CAR-T cell expansion [ 16 ]. (biomedcentral.com)

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)
Furthermore, the anti-tumor activity of the CAR+ T cells numerically expanded on aAPC with or without co-stimulation was tested by adoptive transfer into mice containing CD19+ tumor. (bmj.com)
Conclusions: Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool. (uninsubria.it)
CAR T cell therapy is a form of engineered adoptive cellular therapy that has shown remarkable efficacy in the treatment of cancer, especially hematologic malignancies. (apbmt.org)

cytokine blockade with etanercept and tocilizumab was effective in reversing the syndrome and did not prevent expansion of chimeric antigen receptor T cells or reduce antileukemic efficacy. (nih.gov)
We hypothesized that combined meso-CAR T cells with an oncolytic adenovirus expressing TNF-α and IL-2 (Ad5/3-E2F-D24-TNFa-IRES-IL2, or OAd-TNFa-IL2) would improve efficacy. (jci.org)
These findings indicate that combining cytokine-armed oncolytic adenovirus to enhance the efficacy of CAR T cell therapy is a promising approach to overcome the immunosuppressive TME for the treatment of PDA. (jci.org)
Secondly, ongoing research is focused on optimizing the design and engineering of CAR-T cells to enhance their anti-cancer efficacy while minimizing adverse effects. (bestcollegetutors.com)
Mesenchymal stem cells (MSC) is an important type of cell that is highly acclaimed for their safety and efficacy as a therapeutic agent cells. (hla-dr.com)
HiCAR-T cells showed enhanced cytotoxicity against tumor cells under hypoxia compared to normoxia in vitro and antitumor efficacy comparable to that of conventional CAR-T cells in vivo. (biomedcentral.com)

They carry a special receptor called the T-cell receptor on their surface that recognizes antigens - small protein fragments of bacteria, viruses and infected or cancerous body cells - which are presented by specialized immune complexes. (news-medical.net)
However, how this signaling pathway is activated has remained a mystery until now - despite the fact that the T-cell receptor is one of the most extensively studied receptor protein complexes. (news-medical.net)
the latter are ligands for several of the above matrix protein receptors. (ox.ac.uk)
The primary action of DAG is definitely to activate Protein Kinase C (PKC) which can then activate downstream signaling pathways ultimately leading to the nuclear translocation of important transcription factors AP-1 and NF-κB (examined in Isakov and Altman 2002 In the mean time IP3 engages the IP3 receptor (IP3R) liberating calcium from the endoplasmic reticulum (ER). (ecologicalsgardens.com)
This gene provides instructions for making a protein, called the chimeric antigen receptor (CAR), that attaches to cancer cells. (medlineplus.gov)

The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. (bgu.ac.il)

The T-cell receptor (TCR) is a highly polymorphic surface receptor that allows T-cells to recognize antigenic peptides presented on the major histocompatibility complex (MHC). (eur.nl)
Lastly, using "Grouping of Lymphocyte Interactions by Paratope Hotspots" (GLIPH2), we identify clusters of TCRβ sequences with homologous sequences that potentially recognize the same antigens and contain TCRβs that are persist in SSc patients. (eur.nl)

This novel approach dramatically increased stable gene transfer rate and cell viability and resulted in higher yield of CAR+ T cells without the need of long ex vivo expansion to generate therapeutic doses of CAR+ T cells. (uni-wuerzburg.de)
Prior studies of CAR-dependent T cell effector function evaluated CAR design on T-cell responses in vitro and in vivo. (bmj.com)
Our study assesses the effect ex vivo co-stimulation imparts on in vitro and in vivo effector function of CAR+ T cells. (bmj.com)
These data highlight that the use of co-stimulation in the ex vivo culture could potentially impact the therapeutic potential of CAR+ T cells. (bmj.com)
Fig. 3: Impact of TROG-antigen acquisition on CAR-NK cell phenotype and function in vivo. (nature.com)
Fig. 6: AI-CAR-expressing NK cells showed superior in vivo antitumor activity. (nature.com)
The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo . (oncotarget.com)
Factors predictive of CRS severity include high disease burden, use of a fludarabine/cyclophosphamide ( " FluCy " ) lymphodepleting (LD) chemotherapy regimen, high CAR-T cell dose, and rapid/robust CAR-T cell expansion in vivo 2 . (apbmt.org)
However, despite constitutive B cell expression of CD40 and lymphokine receptors, widespread nonspecific polyclonal B cell activation by activated T cells is seldom observed in vivo. (uthscsa.edu)

Chimeric antigen receptors (CARs) are synthetic proteins expressed on the surface of T cells. (medscape.com)
The data suggest that cell-cell and cell-matrix interactions involving adhesive proteins may be important in OC and FBGC function. (ox.ac.uk)
In cells, mRNA uses the information in genes to create a blueprint for making proteins. (medlineplus.gov)

T cell immune protection plays a pivotal role in the treatment of patients with hematological malignancies. (hindawi.com)
However, T cell exhaustion might lead to the possibility of immune escape of hematological malignancies. (hindawi.com)
However, CAR-T cells can also produce some adverse events after treatment of hematological malignancies, such as cytokine release syndrome (CRS), neurotoxicity, and on-target/off-tumor toxicity, which may cause systemic immune stress inflammation, destruction of the blood-brain barrier, and even normal tissue damage. (hindawi.com)
Traditionally, the treatment of hematological malignancies is administrated by chemotherapy, radiotherapy, and stem cell transplantation. (hindawi.com)
In addition, the isolation and storage of umbilical cord blood hematopoietic stem cells have been used to rebuild the immune system for the treatment of hematological malignancies and might be promising for the dynamic equilibrium expansion of functional T cells [ 12 ]. (hindawi.com)
The recent advancements in Chimeric Antigen Receptor T cell (CAR-T) technology have generated considerable excitement in the medical field, particularly in the treatment of hematological malignancies such as Acute Lymphoblastic Leukemia (ALL). (bestcollegetutors.com)
They have made significant strides in developing and implementing CAR-T cell therapy for the treatment of hematological malignancies. (bestcollegetutors.com)
Through the continuous refinement of protocols and the exploration of advanced engineering techniques, CAR-T cell therapy holds great potential in revolutionizing the treatment of hematological malignancies. (bestcollegetutors.com)

Once infused, the cells continue to expand in number and bind to cancer cells via the engineered receptor, resulting in immunologic cancer cell death. (medscape.com)

T cells are our immune system's customized tools for fighting infectious diseases and tumor cells. (news-medical.net)
The engagement between CAR T cells and tumor cells results in a supraphysiologic immune reaction, which eventually results in tumor cell eradication. (apbmt.org)

In CAR-T therapy, a T-cell-a specific type of cell-is taken from a patient's blood and changed in the laboratory so it will attack cancer cells. (cdc.gov)
White blood cells are removed from the blood, then T-cells are separated and sent to the laboratory so that the cells can be changed to attack cancer cells. (cdc.gov)
In addition, it's an important stimulus for employing the T-cell receptor in a therapeutic context for treating infections, cancer, and autoimmune diseases. (nanotech-now.com)
Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. (elifesciences.org)
PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. (elifesciences.org)
In conclusion, we provide a novel platform for virus-free genetic engineering of CAR T cells that can be broadly applied in T-cell cancer therapy. (uni-wuerzburg.de)
Normally, potentially malignant cells are continuously eliminated by the immune system, but cancer cells can accumulate certain mutations, which allow them to escape these mechanisms [ 2 ]. (nature.com)
Cancer immunotherapies aim to support or boost the patient's immune system to enable the effective clearance of cancer cells. (nature.com)
Proliferating cell nuclear Ag (PCNA) is overexpressed in cancer cells. (bgu.ac.il)
We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack. (bgu.ac.il)
With our existing immuno-oncology portfolio of cutting-edge technologies and expertise, we believe joining forces with Kite Pharma will leverage our targets and their leading CAR T cell platform to advance another new promising therapeutic approach to fight cancer. (gilead.com)
The modified immune cells can specifically attack cancer cells. (medlineplus.gov)

[ 4 ] Persistence of CAR T cells for as long as 3 years has been reported. (medscape.com)
Repertoire overlap analysis revealed that samples taken from the same individual over time shared a high number of TCRβ sequences, indicating a clear temporal persistence of the TCRβ repertoire in CD4+ as well as CD8+ T-cells. (eur.nl)
In conclusion, our results show that CD4+ and CD8+ T-cells are highly persistent in SSc patients over time, and this persistence is likely a result from antigenic selection. (eur.nl)

CAR-modified immune cells are expanded until sufficient cell numbers are attained and are adoptively transferred into the patient to fight malignant cells. (nature.com)

The generation of TCR diversity is similar to that for antibodies and B-cell antigen receptors. (wikipedia.org)

Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). (uninsubria.it)
Although other irritants in the smoke may have contributed to the incident, there is supporting evidence that stable strontium can stimulate the release of histamine from mast cells in vitro (ATSDR 2001e). (cdc.gov)

This phenomenon could be offset by a dual-CAR system incorporating both an activating CAR against the cognate tumor antigen and an NK self-recognizing inhibitory CAR that transferred a 'don't kill me' signal to NK cells upon engagement with their TROG + siblings. (nature.com)
Fig. 2: Impact of antigen-induced self-engagement on CAR-NK effector cell phenotype and function. (nature.com)
BCR microclusters on the surface of ABC cells resemble those generated following antigen engagement of normal B cells. (arizona.edu)
To assess whether antigenic engagement of the BCR is required for the ongoing survival of ABC cells, we developed isogenic ABC cells that differed solely with respect to the IgH V region of their BCRs. (arizona.edu)
Antigen engagement from the T-cell receptor (TCR) induces a rapid and dramatic decondensation of chromatin that is necessary for T-cell activation. (ecologicalsgardens.com)

On their surface, these special white blood cells carry a receptor that recognizes antigens . (news-medical.net)
In this study, we show that the NKp44 receptor recognizes PCNA. (bgu.ac.il)

CAR-T therapy may result in serious side effects including two potentially dangerous syndromes: Cytokine Release Syndrome (CRS) and Immune Cell-Associated Neurotoxicity Syndrome (ICANS). (cdc.gov)
The cytokine-release syndrome and B-cell aplasia developed in both patients. (nih.gov)
The infusion of modified T cells can lead to severe cytokine release syndrome (CRS). (bestcollegetutors.com)
While there are risks associated with CAR-T cell therapy, particularly severe cytokine release syndrome and neurologic toxicities, researchers at UPenn are actively working on strategies to minimize these risks. (bestcollegetutors.com)
Among these, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common complications associated with CAR T cell therapy. (apbmt.org)
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most prominent adverse events of CAR T cell therapy. (apbmt.org)

However, from the beginning of puberty after thymus degeneration, human cytomegalovirus (HCMV) persists due to the chronic activation of cytomegalovirus in humans causing repeated activation of T cells, which is considered the driving factor of human immune aging [ 9 ]. (hindawi.com)
In humans, in 95% of T cells the TCR consists of an alpha (α) chain and a beta (β) chain (encoded by TRA and TRB, respectively), whereas in 5% of T cells the TCR consists of gamma and delta (γ/δ) chains (encoded by TRG and TRD, respectively). (wikipedia.org)

A comparison of the antigen-bound structure captured using cryo-electron microscopy with that of a receptor without antigen provides the first clues to the activation mechanism. (news-medical.net)
The remaining question is how antigen binding could instead lead to T-cell activation. (news-medical.net)
Our structure is a blueprint for future studies on T-cell activation,' Tampé is convinced. (news-medical.net)
Various biological processes including immunoreaction of infection, tumor prevention, and human aging could cause telomere damage, tumor-related stress responses, and T regulatory (Treg) cells activation, which even trigger T cell senescence showing the distinctive phenotypic and functional alternation [ 9 , 10 ]. (hindawi.com)
Currently, three main strategies are applied to restore the activation of senescent T cells, including replacement, restoration, and reprogramming. (hindawi.com)
NK cells express germ-line receptors that are either stimulatory or inhibitory, and the summation of these signals determines activation status ( Caligiuri, 2008 ). (elifesciences.org)
One of the major questions regarding the roles of T-cells is whether expansion and activation of T-cells observed in the diseases pathogenesis is antigen driven. (eur.nl)
These toxicities are believed to be associated with increased activation and migration of T cells into the central nervous system. (bestcollegetutors.com)
T cell activation, for example, needs three steps: (1) The lymphocyte T cell receptor (TCR) interacts with the antigen-loaded class II molecule in the first phase. (pharmacygyan.com)
One of the new emerging mechanisms associated with the progression of clear cell renal cell carcinoma (ccRCC) and other tumors is the immune checkpoint pathway, which consists of cellular interactions that prevent excessive activation of T cells under normal conditions. (oncotarget.com)
Other notable toxicities of CAR T cells include macrophage activation syndrome, cytopenia, and potential organ toxicities. (apbmt.org)
The ability of class II MHC‐mediated signals to enhance Ag‐specific B cell responsiveness to CD40‐mediated signaling may selectively promote the activation of B cell clones capable of cognate interactions with helper T cells. (uthscsa.edu)
2011 These changes are required for T-cell activation clonotypic development and the acquisition of effector functions required for a proper immune Ebastine response. (ecologicalsgardens.com)
Demonstration of antigen to the TCR causes multiple signaling pathways required for T-cell activation (examined in Lin and Weiss 2001 Of particular importance is the activation of phospholipase C (PLCγ1) which hydrolyzes phosphatidyl 4 5 (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3). (ecologicalsgardens.com)

First, T or NK cells are isolated from patient's or donor's blood. (nature.com)

One method is to target senescent T cells which have selective apoptosis function. (hindawi.com)

In 1983, Ellis Reinherz first defined the structure of the human T-cell receptor using anti-idiotypic monoclonal antibodies to T-cell clones, complemented by studies in the mouse by Pippa Marrack and John Kappler. (wikipedia.org)

Binding of a tumor antigen via the scFv activates the T cell in a major histocompatibility-independent manner which leads to a cytotoxic response [ 3 ]. (nature.com)
Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. (bepress.com)

Anatomy32

Organisms14

Diseases5

Chemicals and Drugs130

Analytical, Diagnostic and Therapeutic Techniques and Equipment24

Phenomena and Processes53

Disciplines and Occupations1

Information Science3

Health Care2

CD1916

Express chimeric antigen receptors2

Chimeric antigen receptor-modified2

Extracellular6

Recognition11

Immunotherapy14

Ligand7

Maturation4

Signal transduction2

Specificity2

Lymphoma11

Multiple myeloma2

Human leukocy3

Target antigens2

Molecules9

Immune response3

CTL0193

Proliferation6

Binds2

Lymphoid2

Immunoglobulin3

Clinical15

Bone marrow1

Autologous3

Surface receptors1

Lymphocytes2

Therapies5

Effector T cel1

TCRs4

BCMA3

Adoptive4

Efficacy6

Protein5

Cytotoxicity1

Recognize2

Vivo9

Proteins3

Malignancies8

Immunologic1

Tumor cells2

Cancer12

Persistence3

Malignant cells1

Generation of TCR divers1

Vitro2

Engagement5

Recognizes2

Cytokine Release6

Humans2

Activation14

Patient's1

Selective1

Antibodies1

Activates2