Affinity Enhancement: The Science of Engineering a Proprietary TCR Therapeutic to increase tumor specificity.

Naturally occurring T-cell receptors struggle to recognize cancer proteins. This is because the cancer proteins appear very similar to other proteins within the body, "self-proteins". At Adaptimmune, we have a unique ability to engineer the affinity of the T-cell receptors so that they can recognize cancer proteins and as a result can detect and fight cancer within patients.

T-cell receptors consist of two associated protein chains: the alpha (α) and beta (β) chains. Each of the chains has two regions: a variable region and a constant region. The constant region sits next to the T-cell membrane and the variable region of the two chains binds to the target peptides. The variable region of each TCR chain has three hyper-variable complementarity determining regions, or CDRs. Our technology modifies these CDRs in order to enhance affinity to the cancer cell's HLA peptide complex.

By engineering the sequences that encode the T-cell receptors within a T-cell we can generate a T-cell therapy which works with a patient's own immune system to target specific cancer peptides. Our technology platform allows us to identify and select the T-cell receptors which are likely to prove the most effective in patients whilst minimising off-target (non-cancer cell) binding.