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: 9556596
• 负责人: Christian Hinrichs
• 金额: $ 93.42万
• 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/9556596
• 关键词: Adoptive Transfer; Affinity; Anus; Autologous; Avidity; Cervical; Clinical Trials; Clone Cells; Data Analyses; Epitopes; Genes; HLA-A2 Antigen; HPV-High Risk; Human Papillomavirus; Human papillomavirus 16; Malignant Neoplasms; Malignant neoplasm of anus; Neoplasm Metastasis; Oncoproteins; Oropharyngeal; Patients; Precancerous Conditions; T-Cell Receptor; T-Cell Receptor Genes; T-Lymphocyte; Testing; Vagina; Vulva; cellular transduction; expression vector; gene therapy; 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 has been completed. Data analysis is underway. 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高亲和力的hla - a2限制性TCR，用于对抗HPV-16 E6癌蛋白。这是通过从一名肛门癌患者的转移性肿瘤中鉴定出抗E6 29-38的T细胞克隆来完成的。测定该克隆表达的TCR基因序列，生成编码TCR的逆转录病毒表达载体。经转导表达该TCR的T细胞对HPV-16 E6 29-38表位表现出高亲和力，并对HPV-16阳性肿瘤细胞系具有特异性识别。一项临床试验测试过继性转移的自体T细胞转导，以表达这种TCR治疗hpv阳性癌症已经完成。数据分析正在进行中。此外，我们已经确定了针对HPV-16 E7的TCR。这种TCR的临床试验也在进行中。