Co‐administration of 2’3’-cGAMP STING activator and CpG-C adjuvants with a mutated form of HPV 16 E7 protein leads to tumor growth inhibition in the mouse model

Abstract

Abstract Persistent infection with high-risk genotypes of human papillomavirus (HPV) is the leading cause of cervical cancer. The HPV oncoprotein E7 is constitutively expressed in cervical cancer and considered as an essential target for tumor-specific immunity. The goal of this study was to develop a candidate therapeutic vaccine based on the mutated E7 protein that had possibly reduced transformation capacity while was able to elicit a robust immune response. Therefore, the mutant type of HPV 16 E7 (E7GRG) protein was recombinantly expressed in E. coli. The protein was then purified and formulated with 2’-3’cGAMP CDN and/or CpG-C ODN adjuvants and subcutaneously injected to female C57BL/6 mice. To evaluate the immunogenic response, lymphocyte proliferation, secretion levels of IFN-γ and IL-4 cytokines, granzyme B level, and total IgG and subclasses of IgG antibody were measured. The anti-tumor activity was evaluated in tumor-harboring C57BL/6 mice. The highest rate of cell proliferation, IFN-γ and granzyme B levels, and amount of IgG antibody were found in mice group that were injected by E7GRG + 2′-3′cGAMP + CpG-C. Therapeutic immunization with E7GRG + 2′-3′cGAMP + CpG-C also significantly suppressed TC-1 tumor growth in mice. In conclusion, the results demonstrated that E7GRG + 2′-3′cGAMP + CpG-C induced strong cell-mediated and humoral immune responses that resulted in inhibition of tumor in mouse model.

Keywords

• Human papillomavirus
• HPV vaccine
• E7 oncoprotein
• Stimulator of interferon genes
• STING
• CpG ODN 2395