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

我们已经分离到一株针对HPV-16E6癌蛋白的高亲和力的人类白细胞抗原A2限制性TCR。这是通过从一名肛门癌患者的转移肿瘤中识别出针对E629-38的T细胞克隆来实现的。测定了该克隆表达的TCR基因序列，构建了编码TCR的逆转录病毒表达载体。转导表达该TCR的T细胞对HPV-16E6 29-38表位表现出高亲和力，并对HPV-16阳性肿瘤株具有特异性识别能力。计划进行一项临床试验，测试转导表达这种TCR的自体T细胞过继转移治疗HPV阳性癌症。我们正在研究针对HPV-16和HPV-18E6和E7的各种表位的其他受体，也用于临床试验。

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 planned. We are studying other receptors targeting various epitopes of HPV -16 and HPV-18 E6 and E7, also for use in clinical trials.