CAR-T Cells are a variant of genetically-modified T Cells that can be transfused back to patients as a mode of therapy. It is a set of T cells carrying chimeric antigen receptors and a promising therapeutic in adoptive T cell therapy. Unlike traditional T Cells carrying T cell receptors (TCRs) that only recognize foreign antigens bound to MHC molecules, CAR-T Cells carry artificial antigen-recognizing receptors that don’t require an MHC-peptide complex. These receptors are typically introduced into these T cells via transfection of the receptor-coding gene.

CAR composition:

Extracellular Region:
It is typically encoded genetically as a single-chain variable fragment (scFv) which contain a single variable heavy (VH) and light chain (VL) (as opposed to the variable fragment found on normal immunoglobulins, which has 2 sets of VH, VL). Using modern molecular engineering techniques to modify this region, one can generate a vast number of specific chimeric antigen receptors.





Intracellular Region:
Binding of the target antigen to the extracellular component leads to activation of intracellular signaling pathways. Common insertions here are domains taken from the CD34-1BB (CD137), or other co-stimulatory molecules designed to maximize T Cell survival, proliferation, and anti-tumor responses.





KYMRIAH™/Tisagenlecleucel (Novartis) is the first FDA-approved CAR-T Cell based therapy to treat refractory B acute lymphoblastic leukemia (B-ALL). Tisagenlecleucel engineers CAR-T Cells to target the B Cell marker CD19. Clinical trials have shown statistically significant improvement in survival rates in patients treated with Tisagenlecleucel compared to placebo2.

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Educational References
2. FDA’s statement on the Oncologic Drugs Advisory Committee Meeting- Download the PDF