Unknown

Dataset Information

0

Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6.


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. EXPERIMENTAL DESIGN: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.

SUBMITTER: Draper LM 

PROVIDER: S-EPMC4603283 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6.

Draper Lindsey M LM   Kwong Mei Li M ML   Gros Alena A   Stevanović Sanja S   Tran Eric E   Kerkar Sid S   Raffeld Mark M   Rosenberg Steven A SA   Hinrichs Christian S CS  

Clinical cancer research : an official journal of the American Association for Cancer Research 20151001 19


<h4>Purpose</h4>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.<h4>Experimental design</h4>T-cell responses against the HPV-16 oncoproteins were investigated in a patient with an ongoing  ...[more]

Similar Datasets

| 2177506 | ecrin-mdr-crc
| S-EPMC9620481 | biostudies-literature
| S-EPMC6712783 | biostudies-literature
| S-EPMC7825221 | biostudies-literature
| S-EPMC3927653 | biostudies-literature
| S-EPMC3571619 | biostudies-literature
| S-EPMC7606683 | biostudies-literature
| S-EPMC18715 | biostudies-literature
2024-08-25 | GSE274812 | GEO
| S-EPMC4099350 | biostudies-literature