Fig. 3.

Genetically modified TCRs for cancer immunotherapy. (A) T-cell response can be manipulated and redirected against cancer, with improved specificity and affinity for tumour antigens, via genetic engineering of the endogenous TCR. (B) Genetically modified TCR: gene sequences are transferred to the T cell to encode new TCR α and β chains with different peptide specificity. In addition, there can also be transmembrane changes (red bars). To minimise interchain mispairing with the endogenous TCR, modifications such as the addition of a disulphide bridge (ss) are made. (C) Alternatively, a fusion receptor can be generated, a chimeric antigen receptor (CAR). Typically, these consist of three parts: a recognition sequence [represented here by an antibody-derived single-chain variable fragment (scFv)], a transmembrane element and an intracellular bespoke signalling domain (CD3ζ), which also contains co-stimulatory molecules, such as CD28 and tumour necrosis factor receptors (TNFr) such as OX-40.