T-Cell Receptor (TCR) Engineered Cells and Their Transition to the Clinic

Abstract

Immune-modulatory treatments have shown a great promise in treating patients with advanced or metastatic disease. Currently approved immunotherapy approaches target PD1/PDL1 pathway or use specific autologous T-cells genetically modified to express a chimeric antigen receptor (CAR). Although promising, in most patients with solid malignancies these approaches either do not work or the disease becomes resistant to treatment. Unlike CAR-T cell therapy, genetically modifying T cell receptor T cells (TCR-T) have an advantage of targeting intracellular proteins and expanding number of potential targets. These approaches are limited by recognition of peptides bound to specific MHC molecules. There are currently no approved TCR-T cell products but increasing number of clinical trials are providing us with preliminary efficacy and toxicity data. Encouraging results in reported clinical trials show the potential for impressive and durable responses, but also highlights the challenges of on-target off-tumor toxicities. Current research is focusing on improving efficacy, expanding targets and limiting toxicities. Continual development of multiple products holds a great promise and new technologies aim to improve efficacy, identify novel targets and streamline production to allow larger number of patients to be eligible to be treated with TCR-T cell approaches in the future.KeywordsT cell receptor (TCR)MHCHLACEAMART-1NY-ESO-1gp100Mage-A3Mage-A4NeurotoxicityCardiotoxicity