Chimeric Costimulatory Receptor T Cells (CCR-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. This CAR variant is known as a Chimeric Costimulatory Receptor (CCR). Combining the CCR 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.

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Combining the natural signaling machinery and selectivity of the GD TCR with the targeting ability and costimulatory enhancement of the CCR 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. CCR-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 CCR-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.
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