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

Autor: Sanja Stevanović, Christian S. Hinrichs, Lindsey Draper, Steven A. Rosenberg, Cornelia L. Trimble, Tracy E. Campbell, Benjamin Y. Jin, Bianca Weissbrich, Zhiya Yu, Nicholas P. Restifo
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
CD8 Antigens
medicine.medical_treatment
Genetic enhancement
T cell
Receptors
Antigen
T-Cell
Uterine Cervical Neoplasms
chemical and pharmacologic phenomena
Cervix Uteri
CD8-Positive T-Lymphocytes
Cervical intraepithelial neoplasia
Mice
03 medical and health sciences
0302 clinical medicine
Antigen
Cell Line
Tumor
Animals
Humans
Medicine
Human papillomavirus
Receptor
Papillomaviridae
Cervical cancer
Human papillomavirus 16
business.industry
Papillomavirus Infections
T-cell receptor
Genetic Therapy
General Medicine
Immunotherapy
Uterine Cervical Dysplasia
medicine.disease
Cancer treatment
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Oncology
Murine model
030220 oncology & carcinogenesis
Cancer research
Female
Identification (biology)
business
CD8
Research Article
Zdroj: JCI Insight. 3
ISSN: 2379-3708
Popis: 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).
Databáze: OpenAIRE
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