期刊
JCI INSIGHT
卷 6, 期 7, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.141912
关键词
-
资金
- Intramural Research Program of the Center for Cancer Research, NCI, NIH
- NCI
- Precigen Inc.
The study evaluated the therapeutic gorilla adenovirus HPV vaccine, PRGN-2009, demonstrating promising preclinical antitumor efficacy and induction of HPV-specific T cells in mouse models, providing rationale for further evaluation in clinical trials.
There are approximately 44,000 cases of human papillomavirus-associated (HPV-associated) cancer each year in the United States, most commonly caused by HPV types 16 and 18. Prophylactic vaccines successfully prevent healthy people from acquiring HPV infections via HPV-specific antibodies. In order to treat established HPV-associated malignancies, however, new therapies are necessary. Multiple recombinant gorilla adenovirus HPV vaccine constructs were evaluated in NSG-beta 2m(-/-) peripheral blood mononuclear cell-humanized mice bearing SiHa, a human HPV16(+) cervical tumor, and/or in the syngeneic HPV16(+) TC-1 model. PRGN-2009 is a therapeutic gorilla adenovirus HPV vaccine containing multiple cytotoxic T cell epitopes of the viral oncoproteins HPV 16/18 E6 and E7, including T cell enhancer agonist epitopes. PRGN-2009 treatment reduced tumor volume and increased CD8(+) and CD4(+) T cells in the tumor microenvironment of humanized mice bearing the human cervical tumor SiHa. PRGN-2009 monotherapy in the syngeneic TC-1 model also reduced tumor volumes and weights, generated high levels of HPV16 E6-specific T cells, and increased multifunctional CD8(+) and CD4(+) T cells in the tumor microenvironment. These studies provide the first evaluation to our knowledge of a therapeutic gorilla adenovirus HPV vaccine, PRGN-2009, showing promising preclinical antitumor efficacy and induction of HPV-specific T cells, along with the rationale for its evaluation in clinical trials.
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