Generation of T-cell receptors recognizing antigens on non-melanoma tumors

生成识别非黑色素瘤肿瘤抗原的 T 细胞受体

• 批准号: 9556534
• 负责人: James C Yang
• 金额: $ 94.35万
• 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/9556534
• 关键词: Adoptive Transfer; Alleles; Antigen Targeting; Antigens; Asians; Cells; Clinical; Clinical Trials; Clone Cells; Cloning; Data; Development; Engineering; Enrollment; Epitopes; Generations; Genetic; Genetic Engineering; HLA-A11; Hematopoietic Neoplasms; Human; Immune; Immunologic Receptors; Malignant Neoplasms; Malignant neoplasm of thymus; Malignant neoplasm of thyroid; Mus; Mutate; Mutation; Normal tissue morphology; Oncogenes; Patients; Population; Proteins; Protocols documentation; Reagent; Renal carcinoma; Series; T cell therapy; T-Cell Receptor; T-Lymphocyte; Thyroglobulin; Tumor Suppressor Proteins; Tumor Tissue; actionable mutation; chimeric antigen receptor; immunogenic; melanoma; receptor; receptor function; tumor

We will be collaborating with centers which are generating genetic expression data on both human tumors and normal tissues to seek candidate proteins suitable for immune attack. Thusfar, we have succeeded in generating and optimizing a chimeric antigen receptor targeting CD70, a protein on nearly all human renal cancer, thymic cancers and many blood cancers and an approved protocol is about to start enrolling. In addition, a mouse T-cell receptor that functions well in human T-cells and recognizes human thyroglobulin as a thyroid cancer antigen has been cloned and a clinical procotol for differentiated thyroid cancer is now open to accrual. Currently we are developing T-cell receptor that immunologically recognize consistently mutated driver mutations common in certain human cancers. Two new TCRs specific for G12D and G12V mutations in RAS have been generated which are restricted by HLA-A11 (15% of the US population and the most common Class I allele in some Asian populations). These are poised to enter clinical trials with T-cell adoptive therapy. New anti-mutRAS receptors with other HLA restrictions are in development.

我们将与中心合作，这些中心正在为人类肿瘤和正常组织生成遗传表达数据，以寻求适合免疫攻击的候选蛋白。因此，我们成功地生成和优化了靶向CD70的嵌合抗原受体，这是一种几乎所有人类肾癌，胸腺癌和许多血液癌的蛋白质，并且批准的方案即将开始入学。此外，已经克隆了人类T细胞在人类T细胞中良好起作用并识别人甲状腺球蛋白作为甲状腺癌抗原的小鼠T细胞受体，并且已经克隆了用于分化的甲状腺癌的临床丙糖醇。目前，我们正在开发T细胞受体，这些受体在某些人类癌症中常见的持续突变的驱动器突变在某些人类癌症上始终如一。已经产生了HLA-A11（美国人群的15％，在某些亚洲人群中最常见的I类等位基因）限制了RAS中G12D和G12V突变的两个新的TCR。这些有望通过T细胞产卵疗法进行临床试验。具有其他HLA限制的新的抗毛肌受体正在开发中。