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

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. Hinrichs

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish (US)
JournalJCI Insight
Volume3
Issue number8
DOIs
StatePublished - Apr 19 2018

Keywords

  • Immunology
  • Immunotherapy
  • T cells
  • T-cell receptor

ASJC Scopus subject areas

  • Medicine(all)

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