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.
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.
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.
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. Clin Cancer Res; 21(19); 4431-9. ©2015 AACR.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 Oct 01 [Epub]
Lindsey M Draper, Mei Li M Kwong, Alena Gros, Sanja Stevanović, Eric Tran, Sid Kerkar, Mark Raffeld, Steven A Rosenberg, Christian S Hinrichs
Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. , Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.