T-Cell Receptor Gene Therapy for Human Cancers-Cures

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T cell receptor (TCR) gene therapy is a personalized, cancer treatment strategy that can precisely and potently target a wide variety of tumor antigens. It is based on the infusion of T cells that are genetically engineered ex vivo to express a TCR directed against a tumor antigen. This strategy enables tumor targeting with a large number of T cells that express a high affinity TCR. It also permits pretreatment host conditioning to enhance anti-tumor T cell engraftment and function. TCR gene therapy has shown encouraging results in melanoma, synovial cell sarcoma, and human papillomavirus-associated cancers. In contrast to antibody and chimeric antigen receptor (CAR) therapy, TCR gene therapy can target intracellular antigens, which is important because many of attractive oncological therapeutic targets (e.g. mutated protooncogenes, viral oncogenes, driver chromosomal translocations, and cancer germline antigens) localize to the intracellular compartment. The goal of this NCI Moonshot Project is to catalyze the discovery and development of TCR gene therapy for a wide-array of cancers.