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

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。这是通过从肛门癌患者的转移性肿瘤中鉴定出一个针对E6 29-38表位的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。

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.