• Clinical trials in the early 2010s using second generation CARs targeting CD19, a protein expressed by normal B cells as well as B-cell leukemias and lymphomas, by investigators at the NCI, University of Pennsylvania, and Memorial Sloan Kettering Cancer Center demonstrated the clinical efficacy of CAR T cell therapies and resulted in complete remissions in many heavily pre-treated patients. (wikipedia.org)
  • 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)
  • CAR-T cells, which incorporate an antibody-derived extracellular receptor and T cell derived intracellular signaling domains, have shown convincing outcomes in certain types of leukemia and lymphoma, including commercial licensure of CD19 CAR-Ts for the treatment of relapsed/ refractory large B cell lymphoma and acute lymphoblastic leukemia. (bdbiosciences.com)
  • The technique has also shown preliminarily promising outcomes in B cell acute lymphoblastic leukemia (B-ALL), B cell non-Hodgkin's lymphoma (B-NHL), chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma and multiple myeloma in clinical trials targeting CD19, CD20, CD22, CD30 and B-cell maturation antigen (BCMA), with many more under investigation. (bdbiosciences.com)
  • Blinatumomab is a bispecific T-cell engager (BiTE) targeting CD19 on malignant B cells and CD3 on normal host T cells. (hindawi.com)
  • Relapses of CD19-expressing leukemia in patients who achieved initial remission after CD19 targeting CART cells treatment highly correlates with poor CAR T cells persistence [ 2 ]. (biomedcentral.com)
  • This talk will feature novel mechanisms of resistance to CAR T therapy, novel target antigens and CAR T cell products for treating multiple myeloma, virus-free transposon-based gene-transfer for CAR T manufacturing, and a novel application for CAR T in fungal infections. (pegsummiteurope.com)
  • Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs. (spandidos-publications.com)
  • Small-molecule inhibitors, antagonistic monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bispecific antibodies or biologics (bsAbs) and chimeric antigen receptor-modified T cells (CAR-Ts) targeting Notch signaling components have been developed as investigational anti-cancer drugs ( 10 - 12 ). (spandidos-publications.com)
  • The first chimeric receptors containing portions of an antibody and the T cell receptor was described in 1987 by Yoshihisa Kuwana et al. (wikipedia.org)
  • This work prompted CD3ζ intracellular domains to be added to chimeric receptors with antibody-like extracellular domains, commonly single-chain fraction variable (scFv) domains, as well as proteins such as CD4, subsequently termed first generation CARs. (wikipedia.org)
  • CAR has scFv derived from antibody, containing CD3ζ and costimulatory domain(s), making engineered CAR able to recognize specific tumor associated antigens. (cip.com.cn)
  • ScFv is the antigen-binding domain of CAR structure, which is composed of a single heavy and light chain of monoclonal antibody connected by a linker. (biomedcentral.com)
  • The present invention provides methods of treating, ameliorating, or inhibiting tumor growth, cancer, or pathological angiogenesis by administering to a subject in need thereof a human antibody or fragment thereof that specifically binds to human delta-like ligand 4 (hDll4) and blocks hDll4 binding to a Notch receptor. (justia.com)
  • Antibody-drug conjugates (ADCs) combine the advantages of high targeting of antibody drugs and high activity of Payload in tumor tissues, providing better efficacy than traditional antibody-based therapeutic agents and demonstrating great clinical value. (huatengsci.com)
  • Similar early clinical trials of CAR T cells in solid tumors in the 1990s using first generation CARs targeting a solid tumor antigens such as MUC1 did not show long-term persistence of the transferred T cells or result in significant remissions. (wikipedia.org)
  • One is the ability to administer large numbers of highly selected cells with high avidity for tumor antigens that can recognize shared and patient-specific mutated (neo) antigens. (biomedcentral.com)
  • Unlike antibodies that target extracellular proteins, T cell receptors can target intracellular proteins, processed into peptides, and brought to the surface by HLA. (pegsummiteurope.com)
  • The present invention generally relates to antibodies that bind to NKG2D, including multispecific antigen binding molecules e.g. for activation of T cells and/or NK cells. (justia.com)
  • The present inventors discovered that by forming a large immune complex comprising antigens containing two or more antigenic binding units (epitopes) and two or more antigen-binding molecules (for example, antibodies), elimination from the plasma of the antigens containing two or more antigenic binding units can be accelerated. (justia.com)
  • Immunotherapeutic agents including antibodies and chimeric antigen receptor T cells are widely studied in clinical trials. (biomedcentral.com)
  • A first generation CAR containing a CD4 extracellular domain and a CD3ζ intracellular domain was used in the first clinical trial of chimeric antigen receptor T cells by the biotechnology company Cell Genesys in the mid 1990s, allowing adoptively transferred T cells to target HIV infected cells, although it failed to show any clinical improvement. (wikipedia.org)
  • When they come in contact with their targeted antigen on a cell's surface, CAR T cells bind to it and become activated, then proceed to proliferate and become cytotoxic. (wikipedia.org)
  • 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)
  • There is also a need for rational combinations beyond interleukin (IL)-2 and programmed death (PD)-1/ cytotoxic T-lymphocyte-associated antigen (CTLA)-4 immune checkpoint blockade and to combat exhaustion and restore costimulatory functions, e.g., with gene-engineered or pharmacologic agent-treated TILs. (biomedcentral.com)
  • In biology, chimeric antigen receptors (CARs)-also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors-are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. (wikipedia.org)
  • Modification with chimeric antigen receptors (CARs) endows T cells with tumor specific cytotoxicity and thus induce anti-tumor immunity against malignancies. (ijbs.com)
  • Human derived T lymphocytes engineered to express chimeric antigen receptors, which are expanded in vitro culture and then infused into patients exerting robust cytotoxicity after tumor antigen recognition and subsequent activation. (biomedcentral.com)
  • Due to their structure difference, TCR-T and CAR-T cells show different characteristics in signal activation and antigen recognition. (cip.com.cn)
  • 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 cellular therapy, especially chimeric antigen receptor (CAR) T cell therapy, has gained unprecedented success among hematologic tumors [ 11 ]. (hindawi.com)
  • Even though clinical results are encouraging for both approaches, several major challenges have been identified, including: target antigen selection such as less tumor toxicity and antigen escape, T cell homing to the tumor, T cell infiltration into the tumor, T cell persistence, and local immunosuppression in the tumor microenvironment. (cip.com.cn)
  • Nevertheless, targeting solid tumors is more challenging than targeting hematological malignancies because of tumor histopathological characteristics, shortage of specific antigens and local strong immunosuppressive microenvironment [ 4 ]. (ijbs.com)
  • 1 T cells are engineered to express CARs through viral vectors, enabling them to recognize specific target antigens. (bdbiosciences.com)
  • The CAR programs the recipient's T cells to target an antigen that is present on the surface of tumors. (wikipedia.org)
  • However, targeting solid tumors is more challenging than targeting B-cell malignancies with CAR-T cells because of the histopathological structure features, specific antigens shortage and strong immunosuppressive environment of solid tumors. (ijbs.com)
  • Chimeric antigen receptor-modified T cells for acute lymphoid leukemia[J]. The New England Journal of Medicine , 2013 , 368 (16): 1509-1518. (cip.com.cn)
  • In recent years, engineering T cell therapy has made great progress in tumor immunotherapy, which mainly includes T-cell receptor-engineered T cell (TCR-T) therapy and chimeric antigen receptor T cell (CAR-T) therapy. (cip.com.cn)
  • The immunotherapy field is vibrant with rapid progress being made on the targeting of solid tumours and enhancing effector function. (pegsummiteurope.com)
  • NOTCH1, NOTCH2, NOTCH3 and NOTCH4 are transmembrane receptors that transduce juxtacrine signals of the delta‑like canonical Notch ligand (DLL)1, DLL3, DLL4, jagged canonical Notch ligand (JAG)1 and JAG2. (spandidos-publications.com)
  • Programmed death ligand 1 (PD-L1), a mediator of the PD-1 receptor, plays an inhibitory role in cancer immune responses. (cancer-genetics.org)
  • For safety, CAR T cells are engineered to be specific to an antigen that is expressed on a tumor but is not expressed on healthy cells. (wikipedia.org)
  • However, relapse of primary disease remains a major obstacle after CAR T cells therapy, and the majority of relapses present a tumor phenotype with retention of target antigen (antigen-positive relapse), which highly correlate with poor CAR T cells persistence. (biomedcentral.com)
  • Therefore, CAR has an ability to bind unprocessed tumor surface antigens without MHC processing, while TCR engages with both tumor intracellular and surface antigens embedded in MHC. (cip.com.cn)
  • The interleukin 2 receptor, which is involved in T cell-mediated immune responses, is present in 3 forms with respect to ability to bind interleukin 2. (cancer-genetics.org)
  • The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor. (wikipedia.org)
  • Synthetic biology technologies have enabled flexible reprogramming of engineered T cells to overcome the aforementioned limitations, bringing new opportunities for improving their safety and effectiveness, but the choice of a suitable target antigen is still a key for success. (cip.com.cn)
  • Disease relapse following CAR T cell therapy can be categorized into two major patterns: target antigen loss relapse or antigen-positive relapse. (biomedcentral.com)
  • Moreover, improved preclinical TCR/CAR screening is likely to enhance the safety of engineered T cell therapies, and additional T cell engineering to further enhance engineered T cells at various levels has generated promising results, including: (1) modulation of affinity, (2) safety control elements, and (3) targeting TME components. (cip.com.cn)
  • Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. (cancer-genetics.org)
  • Related T cell approaches such as engineered T cell receptors also show promise. (bdbiosciences.com)
  • The surface of CAR T cells can bear either of two types of co-receptors, CD4 and CD8. (wikipedia.org)