T-cell receptor gene therapy for human papillomavirus-positive cancers

T 细胞受体基因疗法治疗人乳头瘤病毒阳性癌症

• 批准号: 9343949
• 负责人: Christian Hinrichs
• 金额: $ 105.62万
• 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/9343949
• 关键词: Adoptive Transfer; Affinity; Anus; Autologous; Avidity; Clinical Trials; Epitopes; Genes; HLA-A2 Antigen; Human Papillomavirus; Human papillomavirus 16; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Neoplasm Metastasis; Oncogenes; Oropharyngeal; Patients; T-Cell Receptor; T-Cell Receptor Genes; T-Lymphocyte; Testing; Vagina; Vulva; expression vector; gene therapy; high risk; receptor; tumor

We have isolated a high-affinity HLA-A2-restricted TCR against the HPV-16 E6 oncoprotein. This was accomplished by identifying from the metastatic tumor of a patient with anal cancer a T cell clone against the E6 29-38. The gene sequence of the TCR expressed by this clone was determined, and a retroviral expression vector encoding the TCR was generated. T cells transduced to express this TCR display high-avidity for the HPV-16 E6 29-38 epitope as well as specific recognition of HPV-16-positive tumor lines. A clinical trial testing adoptive transfer of autologous T cells transduced to express this TCR for the treatment of HPV-positive cancers is active. In addition, we have identified a TCR targeting HPV-16 E7. A clinical trial of this TCR is also active.

我们已经分离出一种针对HPV-16 E6癌蛋白的高亲和力HLA-A2限制性TCR。这是通过从肛门癌患者的转移性肿瘤中鉴定针对E6 29-38的T细胞克隆来实现的。确定由该克隆表达的TCR的基因序列，并产生编码TCR的逆转录病毒表达载体。经转导以表达该TCR的T细胞显示出对HPV-16 E6 29-38表位的高亲合力以及对HPV-16阳性肿瘤系的特异性识别。测试用于治疗HPV阳性癌症的经转导以表达该TCR的自体T细胞的过继转移的临床试验是活跃的。此外，我们已经鉴定了靶向HPV-16 E7的TCR。这种TCR的临床试验也在进行中。