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.


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