T-Cell Receptor Gene Therapy for Human Cancers-Cures

T 细胞受体基因疗法治疗人类癌症

• 批准号: 10487027
• 负责人: James L. Gulley
• 金额: $ 405.11万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487027
• 关键词: Affinity; Antibodies; Antigens; Chromosomal translocation; Clinical Trials; Common Neoplasm; Engraftment; Epitopes; Goals; Human; Human Papilloma Virus-Related Malignant Neoplasm; Infusion procedures; Malignant Neoplasms; Mutate; Proto-Oncogenes; Safety; Signal Transduction; T cell therapy; T-Cell Development; T-Cell Receptor; T-Cell Receptor Genes; T-Lymphocyte; T-Lymphocyte Epitopes; Therapeutic; Tumor Antigens; Viral Oncogene; base; cancer therapy; chimeric antigen receptor; conditioning; gene therapy; genetically modified cells; melanoma; personalized cancer therapy; synovial sarcoma; targeted treatment; therapeutic target; treatment strategy; tumor

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.

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各种肿瘤抗原。它基于T细胞的输注，所述T细胞经离体遗传工程改造以表达针对肿瘤抗原的TCR。这种策略使得能够用表达高亲和力TCR的大量T细胞靶向肿瘤。它还允许预处理宿主调节以增强抗肿瘤T细胞植入和功能。TCR基因疗法在黑色素瘤、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）疗法相反，TCR基因疗法可以靶向细胞内抗原，这是重要的，因为许多有吸引力的肿瘤治疗靶标（例如突变的原癌基因、病毒癌基因、驱动染色体易位和癌症生殖系抗原）定位于细胞内区室。NCI Moonshot项目的目标是促进TCR基因疗法的发现和开发，用于各种癌症。