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

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的29-38表位的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。计划进行一项临床试验，测试转导以表达该TCR的自体T细胞的过继转移，用于治疗HPV阳性癌症。

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 29-38 epitope of E6. 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.