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.
|Hinrichs, Christian S (2016) Molecular Pathways: Breaking the Epithelial Cancer Barrier for Chimeric Antigen Receptor and T-cell Receptor Gene Therapy. Clin Cancer Res 22:1559-64|
|Draper, Lindsey M; Kwong, Mei Li M; Gros, Alena et al. (2015) Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6. Clin Cancer Res 21:4431-9|