TY - JOUR
T1 - Intranasal therapeutic peptide vaccine promotes efficient induction and trafficking of cytotoxic t cell response for the clearance of HPV vaginal tumors
AU - Sierra, Gloria
AU - Dorta-Estremera, Stephanie
AU - Hegde, Venkatesh L.
AU - Nookala, Sita M.K.
AU - Yanamandra, Ananta V.
AU - Sastry, K. Jagannadha
N1 - Funding Information:
Acknowledgments: HPV + TC-1-Luc cell line was a kind gift from Wu, T.-C. and Hung, C. (Johns Hopkins School of Medicine, Baltimore, MD, USA). We’d like to also acknowledge The Small Animal Imaging Facility and the South Campus Flow Cytometry and Cell Sorting Core at MD Anderson Cancer Center are supported by NIH (NCI P30 CA016672).
Funding Information:
This research was funded by the HPV-related Cancers Moon Shot Program of the University of Texas MD Anderson Cancer Center and Cancer Prevention and Research Institute of Texas (CPRIT), grant number RP180472 awarded to K.J.S. HPV + TC-1-Luc cell line was a kind gift from Wu, T.-C. and Hung, C. (Johns Hopkins School of Medicine, Baltimore, MD, USA). We?d like to also acknowledge The Small Animal Imaging Facility and the South Campus Flow Cytometry and Cell Sorting Core at MD Anderson Cancer Center are supported by NIH (NCI P30 CA016672).
Funding Information:
Funding: This research was funded by the HPV-related Cancers Moon Shot Program of the University of Texas MD Anderson Cancer Center and Cancer Prevention and Research Institute of Texas (CPRIT), grant number RP180472 awarded to K.J.S.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/6
Y1 - 2020/6
N2 - Human papillomavirus (HPV)-induced cancers continue to affect millions of women around the world, and the five year survival rate under the current standard of care for these cancers is less than 60% in some demographics. Therefore there is still an unmet need to develop an effective therapy that can be easily administered to treat established HPV cervical cancer lesions. We sought to investigate the potential of an intranasal HPV peptide therapeutic vaccine incorporating the combination of α-Galactosylceramide (α-GalCer) and CpG-ODN adjuvants (TVAC) against established HPV genital tumors in a syngeneic C57BL/6J mouse model. We obtained evidence to show that TVAC, delivered by the mucosal intranasal route, induced high frequencies of antigen-specific CD8 T cells concurrent with significant reduction in the immunosuppressive regulatory T cells and myeloid derived suppressor cells in the tumor microenvironment (TME), correlating with sustained elimination of established HPV genital tumors in over 85% of mice. Inclusion of both the adjuvants in the vaccine was necessary for significant increase of antigen-specific CD8 T cells to the tumor and antitumor efficacy because vaccination incorporating either adjuvant alone was inefficient. These results strongly support the utility of the TVAC administered by needle-free intranasal route as a safe and effective strategy for the treatment of established genital HPV tumors.
AB - Human papillomavirus (HPV)-induced cancers continue to affect millions of women around the world, and the five year survival rate under the current standard of care for these cancers is less than 60% in some demographics. Therefore there is still an unmet need to develop an effective therapy that can be easily administered to treat established HPV cervical cancer lesions. We sought to investigate the potential of an intranasal HPV peptide therapeutic vaccine incorporating the combination of α-Galactosylceramide (α-GalCer) and CpG-ODN adjuvants (TVAC) against established HPV genital tumors in a syngeneic C57BL/6J mouse model. We obtained evidence to show that TVAC, delivered by the mucosal intranasal route, induced high frequencies of antigen-specific CD8 T cells concurrent with significant reduction in the immunosuppressive regulatory T cells and myeloid derived suppressor cells in the tumor microenvironment (TME), correlating with sustained elimination of established HPV genital tumors in over 85% of mice. Inclusion of both the adjuvants in the vaccine was necessary for significant increase of antigen-specific CD8 T cells to the tumor and antitumor efficacy because vaccination incorporating either adjuvant alone was inefficient. These results strongly support the utility of the TVAC administered by needle-free intranasal route as a safe and effective strategy for the treatment of established genital HPV tumors.
KW - Adjuvants
KW - Human papillomavirus
KW - Intranasal immunization
KW - Mucosal immunity
KW - Therapeutic vaccine
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U2 - 10.3390/vaccines8020259
DO - 10.3390/vaccines8020259
M3 - Article
C2 - 32485935
AN - SCOPUS:85085622674
SN - 2076-393X
VL - 8
JO - Vaccines
JF - Vaccines
IS - 2
M1 - 259
ER -