Control of Spontaneous HPV16 E6/E7 Expressing Oral Cancer in HLA-A2 (AAD) Transgenic Mice with Therapeutic HPV DNA Vaccine

Ssu-Hsueh Tseng; Li Liu; Shiwen Peng; Jinhwi Kim; Louise Ferrall; Chien-Fu Hung; T. -C. Wu

doi:10.1186/s12929-021-00759-x

Journal of Biomedical Science (Sep 2021)

Control of Spontaneous HPV16 E6/E7 Expressing Oral Cancer in HLA-A2 (AAD) Transgenic Mice with Therapeutic HPV DNA Vaccine

Ssu-Hsueh Tseng,
Li Liu,
Shiwen Peng,
Jinhwi Kim,
Louise Ferrall,
Chien-Fu Hung,
T. -C. Wu

Affiliations

Ssu-Hsueh Tseng: Department of Pathology, Johns Hopkins University, CRB II
Li Liu: Department of Pathology, Johns Hopkins University, CRB II
Shiwen Peng: Department of Pathology, Johns Hopkins University, CRB II
Jinhwi Kim: Department of Obstetrics and Gynecology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
Louise Ferrall: Department of Pathology, Johns Hopkins University, CRB II
Chien-Fu Hung: Department of Pathology, Johns Hopkins University, CRB II
T. -C. Wu: Department of Pathology, Johns Hopkins University, CRB II

DOI: https://doi.org/10.1186/s12929-021-00759-x
Journal volume & issue: Vol. 28, no. 1
pp. 1 – 12

Abstract

Read online

Abstract Background Human Papillomavirus type 16 (HPV16) has been associated with a subset of head and neck cancers. Two HPV encoded oncogenic proteins, E6 and E7, are important for the malignant progression of HPV-associated cancers. A spontaneous HPV16 E6/E7-expressing oral tumor model in human HLA-A2 (AAD) transgenic mice will be important for the development of therapeutic HPV vaccines for the control of HPV-associated head and neck cancers. Methods In the current studies, we characterized the HLA-A2 restricted HPV16 E7-specific CD8 + T cell mediated immune responses in the HLA-A2 (AAD) transgenic mice using a therapeutic naked DNA vaccine encoding calreticulin (CRT) linked to a mutated E7(N53S). We also employed oncogenic DNA plasmids that encoded HPV16E6/E7/Luc, NRasG12V, and sleeping beauty transposase for the transfection into the submucosal of oral cavity of the transgenic mice with electroporation to create a spontaneous oral tumor. Furthermore, we characterized the therapeutic antitumor effects of CRT/E7(N53S) DNA vaccine using the spontaneous HPV16 E6/E7-expressing oral tumor model in HLA-A2 (AAD) transgenic mice. Results We found that CRT/E7(N53S) DNA vaccine primarily generated human HPV16 E7 peptide (aa11-20) specific CD8 + T cells, as compared to the wild-type CRT/E7 vaccine, which primarily generated murine H-2Db restricted E7 peptide (aa49-57) specific CD8 + T cell responses. We also observed transfection of the oncogenic DNA plasmids with electroporation generated spontaneous oral tumor in all of the injected mice. Additionally, treatment with CRT/E7(N53S) DNA vaccine intramuscularly followed by electroporation resulted in significant antitumor effects against the spontaneous HPV16 E6/E7-expressing oral tumors in HLA-A2 (AAD) transgenic mice. Conclusions Taken together, the data indicated that the combination of HPV16 E6/E7-expressing DNA, NRasG12V DNA and DNA encoding sleeping beauty transposase is able to generate spontaneous oral tumor in HLA-A2 (AAD) transgenic mice, which can be successfully controlled by treatment with CRT/E7(N53S) DNA vaccine. The translational potential of our studies are discussed.

Published in Journal of Biomedical Science

ISSN: 1021-7770 (Print); 1423-0127 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine
Website: https://jbiomedsci.biomedcentral.com/

About the journal

Abstract

Keywords