T-Cell Receptor Gene Therapy for Human Cancers-Cures

T细胞受体(TCR)基因治疗是一种个性化的癌症治疗策略，可以精确和有效地靶向多种肿瘤抗原。它是基于体外基因工程T细胞的输注，以表达针对肿瘤抗原的TCR。这一策略使大量表达高亲和力TCR的T细胞能够靶向肿瘤。它还允许对宿主进行预处理，以增强抗肿瘤T细胞的植入和功能。TCR基因治疗在黑色素瘤、滑膜细胞肉瘤和人乳头瘤病毒相关癌症中显示出令人鼓舞的结果。与抗体和嵌合抗原受体(CAR)治疗相比，TCR基因治疗可以靶向细胞内抗原，这一点很重要，因为许多有吸引力的肿瘤治疗靶点(如突变的原癌基因、病毒癌基因、驱动染色体易位和癌症生殖系抗原)定位于细胞内。NCI登月计划的目标是促进TCR基因疗法的发现和发展，以治疗多种癌症。

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.