The Anticancer Potential of T Cell Receptor-Engineered T Cells

Adoptively transferred T cell receptor (TCR)-transgenic T cells (TCR-T cells) are not restricted by cell surface expression of their targets and are therefore poised to become a main pillar of cellular cancer immunotherapies. Addressing clinical and laboratory data, we discuss emerging features for the efficient deployment of novel TCR-T therapies, such as selection of ideal TCRs targeting validated epitopes with well-characterized cancer cell expression and processing, enhancing TCR-T effector function, trafficking, expansion, persistence, and memory formation by strategic selection of substrate cells, and gene-engineering with synthetic co-stimulatory circuits. Overall, a better understanding of the relevant mechanisms of action and resistance will help prioritize the vast array of potential TCR-T optimizations for future clinical products.

Automated summary

Adoptively transferred TCR-transgenic T cells are not restricted by cell surface expression of targets and have the potential to play a key role in cellular cancer immunotherapies. By selecting ideal TCRs, enhancing TCR-T function, expansion, memory formation, and gene-engineering strategies, novel TCR-T therapies can be efficiently deployed.