TY - JOUR AU - Jin, Benjamin Y. AU - Campbell, Tracy E. AU - Draper, Lindsey M. AU - Stevanović, Sanja AU - Weissbrich, Bianca AU - Yu, Zhiya AU - Restifo, Nicholas P. AU - Rosenberg, Steven A. AU - Trimble, Cornelia L. AU - Hinrichs, Christian S. T1 - Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model PY - 2018/04/19/ AB - T cell receptor (TCR) T cell therapy is a promising cancer treatment modality. However, its successful development for epithelial cancers may depend on the identification of high-avidity TCRs directed against tumor-restricted target antigens. The human papillomavirus (HPV) E7 antigen is an attractive therapeutic target that is constitutively expressed by HPV+ cancers but not by healthy tissues. It is unknown if genetically engineered TCR T cells that target E7 can mediate regression of HPV+ cancers. We identified an HPV-16 E7-specific, HLA-A*02:01-restricted TCR from a uterine cervix biopsy from a woman with cervical intraepithelial neoplasia. This TCR demonstrated high functional avidity, with CD8 coreceptor–independent tumor targeting. Human T cells transduced to express the TCR specifically recognized and killed HPV-16+ cervical and oropharyngeal cancer cell lines and mediated regression of established HPV-16+ human cervical cancer tumors in a mouse model. These findings support the therapeutic potential of this approach and established the basis for an E7 TCR gene therapy clinical trial in patients with metastatic HPV+ cancers (NCT02858310). JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.99488 VL - 3 IS - 8 UR - https://doi.org/10.1172/jci.insight.99488 PB - The American Society for Clinical Investigation ER -