Chimeric Costimulatory Receptor T Cells (Co-stim CAR-T)

At TCB, we apply CAR-T technology to GDT cells, taking advantage of the endogenous gamma delta TCR (T cell receptor), and combining it with the high affinity binders of CAR-T. This takes the form of 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 the natural pan-cancer TCR-signaling from a GDT is at the heart of our unique CAR-T approach and the associated IP is exclusively owned by TCB.


Combining the natural signaling machinery and selectivity of the GD TCR with the targeting ability and costimulatory enhancement of the costimulatory receptor into a natural “AND gate”, is powerful and offers several advantages:

  • 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 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 signalling 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 the actual CAR-T treatment could 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 to affect ADCC-mediated killing of the target cell.