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Co-Stim CAR-T

Chimeric Co-stimulatory Receptor T Cells

At TC BioPharm, we apply chimeric antigen receptor T cell (CAR-T) technology to gamma delta T (GDT) cells. This takes advantage of the endogenous gamma delta T cell receptor (TCR), and combines it with chimeric antigen receptors. This involves adding a transgene to the GDT cells which encodes for a truncated version of a conventional CAR, one which doesn’t contain a CD3ζ activating signal component. Combining the co-stim CAR with natural pan-cancer TCR-signaling from a GDT is at the heart of our unique CAR-T approach. The associated IP is exclusively owned by TC BioPharm. Our approach produces a CAR-T product with fewer side effects than conventional CAR-T.

Chimeric Co-stimulatory Receptor T Cells

Co stim left
Co stim right

Combining the natural signaling machinery and selectivity of the gamma delta TCR with the additional co-stimulatory signaling of the chimeric receptor, provides a powerful, yet selective therapeutic that offers several key advantages over other immunotherapies:

  • Healthy cells which express the target antigen are not killed, which eliminates off-tumor toxicity - a transformational advance in CAR-T.
  • The potency of the cell killing is additive so innate GDT cell cytotoxicity is significantly enhanced. Co-stim CAR-T cells are extremely effective at killing targeted cells.
  • Without collateral damage or hyperactive stimulation and by using the natural T cell signaling pathway, the likelihood for serious side-effects associated with cytokine release is reduced.
  • If healthy cells are spared then the significant burden of treatment before and after CAR-T treatment can be dramatically reduced compared with conventional CAR-T. For example, healthy B cells can co-exist with a CD19-directed co-stim CAR-T.
  • Selection of target antigen can be greatly broadened as expression on healthy cells can be tolerated.
  • Antigen escape is less likely due to innate killing, and can be countered by combination with a targeted monoclonal antibody to affect antibody dependent cellular cytotoxicity-mediated killing of the target cell.

Mechanism of Action