Drug name: CAR-T Cell Therapy


Related CSCTT Targets

CD133+ Glioblastoma cells [ref.1]
EpCAM [ref.2]P16422

Introduction

T-cells can recognize and kill tumour cells by using similar mechanisms as for eradicating virally infected cells. T-cells kill their targets through induction of apoptosis, either via death receptors or by secretion of granzymes and perforin[1].

Chimeric antigen receptors (CARs) are human leukocyte antigen (HLA)-independent fusion molecules that couple the binding of a native tumour-associated target, displayed on the surface of tumour cells, to the delivery of a tailored T-cell activating signal. T-cells genetically engineered to express CAR receptors efficiently recognize and kill their target cells. Since an antibody scFv is used to retarget the T-cell, they can be targeted to any available cell surface marker on the tumour cell[1,2].

CAR T-cells can be easily engineered from patient blood and reinfused to the patient after ex vivo expansion. Most of the CARs in current clinical trials join an extracellular single-chain variable fragment (scFv) with the T cell receptor CD3ζ signaling domain as well as an additional domain, CD28 or 4-1BB, to supply a co-stimulatory signal, which appears to be vital for in vivo expansion and persistence[3].

[1] Karlsson, H. (2016). "Approaches to augment CAR T-cell therapy by targeting the apoptotic machinery." Biochem Soc Trans 44(2): 371-376.
[2] Whilding, L. M., et al. (2016). "The integrin alphavbeta6: a novel target for CAR T-cell immunotherapy?" Biochem Soc Trans 44(2): 349-355.
[3] Singh, N., et al. (2016). "CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia." Curr Treat Options Oncol 17(6): 28.

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Reference

  • [1] Rapid and efficient transfer of the T cell aging marker CD57 from glioblastoma stem cells to CAR T cells.
    Zhu, X. and G. Niedermann (2015). Oncoscience 2(5): 476-482. [ 26097880 ]
  • [2] Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM.
    Deng, Z., et al. (2015). BMC Immunol 16: 1. [ 25636521 ]

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