The basic principles of chimeric antigen receptor (CAR) design

By Michel Sadelain, R. Brentjens, I. Rivière. Cancer Discovery, 2013

1,379 citations recorded by the source corpus.

CARs are recombinant receptors that provide both antigen-binding and T cell activating functions. A multitude of CARs has been reported over the past decade, targeting an array of cell surface tumor antigens. Their biological functions have dramatically changed following the introduction of tri-partite receptors comprising a costimulatory domain, termed second generation CARs. These have recently demonstrated clinical benefit in patients treated with CD19-targeted autologous T cells. CARs may be combined with costimulatory ligands, chimeric costimulatory receptors or cytokines to further enhance T cell potency, specificity and safety. CARs represent a new class of drugs with exciting potential for cancer immunotherapy.

Subfields: Immunology, Oncology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/8ea5a00392d640918be9ab989310a719c0ce1c86

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Citations in the corpus

Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. (2016, background): “org Volume 126 Number 8 August 2016 Introduction Chimeric antigen receptors (CARs) are synthetic receptors that retarget T cells to tumor surface antigens (1, 2).”
Remote control of therapeutic T cells through a small molecule-gated chimeric receptor (2015, background): “Patient-topatient variations in T cell responses and in risks for toxicity make it challenging to predict the optimal number of T cells to infuse (2).”
Natural Killer Cells: Development, Maturation, and Clinical Utilization (2018, background): “Through the manipulation of signaling motifs critical for lymphocyte activation, CARs are also designed to utilize specific intracellular signaling molecules which can further refine NK cell function and optimize their therapeutic potential (328, 329).”
Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. (2016, background): “This led to the development of second- and third-generation CARs that incorporate additional costimulatory cytoplasmic domains such as CD28, 4-1BB (CD137), ICOS, and OX40 either individually or in combination (Dotti et al., 2014; Sadelain et al., 2013).”
CAR-T cell therapy: current limitations and potential strategies (2021, background): “One strategy to ameliorate these limitations is through the utilization of delivery routes other than systemic delivery as local administration (1) eliminates the need for CAR-T cells to traffic to disease sites and (2) limits on-target off-tumor toxicities as the CAR-T cells’ on-target activity is ”
Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia (2014, background): “CARs are artificial receptors that redirect antigen specificity, activate T cells, and further enhance T cell function through their costimulatory component (4, 5).”
Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management (2018, background): “CARs with costimulatory domains have increased efficacy compared to first-generation CARs [3,49,65].”