T Cell Receptors (TCRs)

Our high-affinity TCR technology has the potential to recognize proteins expressed inside cancer cells or proteins on the cell surface, which may allow us to target a broad range of tumors. The gene sequence we introduce into T cells with our TCR technology encodes for the proteins required to assemble a TCR that recognizes a specific major histocompatibility complex (MHC) / peptide structure. Beyond the fact that TCRs can recognize peptides derived from intracellular proteins, another advantage of TCRs is that they are fully human and therefore may be less likely to elicit an immune response against the infused TCR cells.

The engagement of a TCR is restricted to a certain MHC type. Due to the variability of MHC types across the human population, different TCRs will be required for various segments of the population. Our TCR constructs are selected by screening healthy donors for naturally-occurring high-affinity TCRs against a MHC/peptide combination of interest. Depending on the binding affinity of the selected TCR construct, it is either used directly or modified by mutating a specific region, the hypervariable domain, of the TCR binding pocket to create a higher affinity construct. Based on the limited number of patients who have received any TCR treatment to date, these TCR cells appear to behave like endogenous T cells after re-infusion back into the patient. They undergo a process similar to an endogenous T cell of multiplication and cytotoxic activation upon recognition of their defined cancer-associated proteins.