Identification of small molecule enhancers of CAR-T cell killing activity

CAR-T细胞杀伤活性小分子增强剂的鉴定

• 批准号: 10005002
• 负责人: Matthew Hall
• 金额: $ 4.76万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 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/10005002
• 关键词: Acute Lymphocytic Leukemia; Adjuvant Therapy; Adult; Back; Biological Assay; CAR T cell therapy; Cancer Patient; Cell Line; Child; Effectiveness; Enhancers; FDA approved; Goals; Hematologic Neoplasms; Lymphoma; Malignant neoplasm of liver; Patients; Reporter; Solid Neoplasm; T-Lymphocyte; cancer immunotherapy; cell killing; chimeric antigen receptor; chimeric antigen receptor T cells; high throughput screening; small molecule; success; synergism

CAR-T cell therapy has seen considerable success in the treatment of hematologic malignancies. In 2017, two CAR T-cell therapies were approved by the FDA, one for children with acute lymphoblastic leukemia (ALL) and the other for adults with advanced lymphomas. However, the potential effectiveness of CAR-T therapies against solid tumors is still somewhat unknown. This project aims to identify small molecules capable of enhancing the killing activity of CAR-T cells, with a particular focus on liver cancers expressing a newly identified promising CAR-T target. The project team has outlined a critical assay path, and begun creating and optimizing a reporter cell line to enable high-throughput screening in conjunction with CAR-T cell treatment to identify compounds with potential additivity/synergy.

CAR-T细胞疗法在治疗血液恶性肿瘤方面取得了相当大的成功。2017年，FDA批准了两种CAR - t细胞疗法，一种用于急性淋巴细胞白血病（ALL）儿童，另一种用于晚期淋巴瘤成人。然而，CAR-T疗法对实体瘤的潜在疗效仍然未知。