Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model

• DOI: 10.1172/jci.insight.99488
• Publication Date: 2018-04-18T15:02:49Z
• Authors: Benjamin Y. Jin; Tracy E. Campbell; Lindsey M. Draper; Sanja Stevanović; Bianca Weissbrich; Zhiya Yu; Nicholas P. Restifo; Steven A. Rosenberg; Cornelia L. Trimble; Christian S. Hinr...
• Keywords: Avidity

T cell receptor (TCR) 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 an attractive therapeutic that constitutively expressed by HPV+ but not healthy tissues. It unknown if genetically engineered TCR cells can mediate regression cancers. We identified HPV-16 E7-specific, HLA-A*02:01-restricted from uterine cervix biopsy woman with cervical intraepithelial neoplasia. This demonstrated high functional avidity, CD8 coreceptor–independent tumor targeting. Human transduced to express specifically recognized and killed HPV-16+ oropharyngeal lines mediated established tumors in mouse model. These findings support potential this approach basis gene clinical trial patients metastatic (NCT02858310).