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 journalArticle

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

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T-Lymphocytes
T-Cell Antigen Receptor
Human papillomavirus 16
Neoplasms
Uterine Cervical Neoplasms
Oropharyngeal Neoplasms
T-Cell Receptor Genes
Antigens
Cervical Intraepithelial Neoplasia
HLA-A Antigens
Cell- and Tissue-Based Therapy
Cervix Uteri
Genetic Therapy
Therapeutics
Clinical Trials
Biopsy
Cell Line

Keywords

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

Cite this

Jin, B. Y., Campbell, T. E., Draper, L. M., Stevanović, S., Weissbrich, B., Yu, Z., ... Hinrichs, C. S. (2018). Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. JCI insight, 3(8). https://doi.org/10.1172/jci.insight.99488

Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. / Jin, Benjamin Y.; Campbell, Tracy E.; Draper, Lindsey M.; Stevanović, Sanja; Weissbrich, Bianca; Yu, Zhiya; Restifo, Nicholas P.; Rosenberg, Steven A.; Trimble, Cornelia L; Hinrichs, Christian S.

In: JCI insight, Vol. 3, No. 8, 19.04.2018.

Research output: Contribution to journalArticle

Jin, BY, Campbell, TE, Draper, LM, Stevanović, S, Weissbrich, B, Yu, Z, Restifo, NP, Rosenberg, SA, Trimble, CL & Hinrichs, CS 2018, 'Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model', JCI insight, vol. 3, no. 8. https://doi.org/10.1172/jci.insight.99488
Jin, Benjamin Y. ; Campbell, Tracy E. ; Draper, Lindsey M. ; Stevanović, Sanja ; Weissbrich, Bianca ; Yu, Zhiya ; Restifo, Nicholas P. ; Rosenberg, Steven A. ; Trimble, Cornelia L ; Hinrichs, Christian S. / Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. In: JCI insight. 2018 ; Vol. 3, No. 8.
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