Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6

Lindsey M. Draper, Mei Li M Kwong, Alena Gros, Sanja Stevanović, Eric Tran, Sid Kerkar, Mark Raffeld, Steven A. Rosenberg, Christian S. Hinrichs

Research output: Contribution to journalArticle

Abstract

Purpose: The E6 and E7 oncoproteins of HPV-associated epithelial cancers are in principle ideal immunotherapeutic targets, but evidence that T cells specific for these antigens can recognize and kill HPV+ tumor cells is limited. We sought to determine whether TCR gene engineered T cells directed against an HPV oncoprotein can successfully target HPV+ tumor cells. ExperimentalDesign: T-cell responses against the HPV-16 oncoproteins were investigated in a patient with an ongoing 22-month disease-free interval after her second resection of distant metastatic anal cancer. T cells genetically engineered to express an oncoprotein-specific TCR from this patient's tumor-infiltrating T cells were tested for specific reactivity against HPV+ epithelial tumor cells. Results: We identified, from an excised metastatic anal cancer tumor, T cells that recognized an HLA-A∗02:01-restricted epitope of HPV-16 E6. The frequency of the dominant T-cell clonotype from these cells was approximately 400-fold greater in the patient's tumor than in her peripheral blood. T cells genetically engineered to express the TCR from this clonotype displayed high avidity for an HLA-A∗02:01-restricted epitope of HPV-16, and they showed specific recognition and killing of HPV-16+ cervical, and head and neck cancer cell lines. Conclusions: These findings demonstrate that HPV-16+ tumors can be targeted by E6-specific TCR gene engineered T cells, and they provide the foundation for a novel cellular therapy directed against HPV-16+ malignancies, including cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers.

Original languageEnglish (US)
Pages (from-to)4431-4439
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number19
DOIs
Publication statusPublished - Oct 1 2015
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Draper, L. M., Kwong, M. L. M., Gros, A., Stevanović, S., Tran, E., Kerkar, S., ... Hinrichs, C. S. (2015). Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6. Clinical Cancer Research, 21(19), 4431-4439. https://doi.org/10.1158/1078-0432.CCR-14-3341