Studies On The Anti-cancer Activity Of A Novel Dual-functional HPV Therapeutic Fusion Protein Vaccine

Human papillomaviruses (HPV), particularly HPV 16, is not only causally linked to cervical cancers but also play an important role in the development of other cancers.The prophylactic HPV vaccine cannot control already-established HPV infections, thus it is very important to develop the efficient and safe HPV therapeutic vaccine for the treatment of HPV-associated cancer. Protein-based HPV therapeutic vaccines are an appealing strategy because of their simplicity, safety and capacity for repeated administration. Researcher is focus on developing new approaches to further enhance vaccine efficacy. Heat shock proteins (HSP), including calreticulin (CRT) and HSP70, have been shown to act as potent immunoadjuvant to enhance antigen-specific anti-tumor immunity, respectively. Futhermore, Previous studies have shown that N domain CRT (NCRT) or C-terminal half of HSP70 (hsp) linked with HPV 16 E7 are capable of inducing potent antigen-specific CTL activity in experimental animal models.Therefore, we have developed a recombinant NCRT/E7/hsp fusion protein to investigate the synergistic effects of NCRT and hsp for enhancing the potency of HPV16 E7 therapeutic vaccine and evaluated the immune responses induced by this fusion protein. In addition, given the potential benefit of NCRT inhibition of angiogenesis, we also determined the antiangiogenic effect of NCRT/E7/hsp fusion protein. Our results demonstrated that NCRT and hsp synergistically exhibited significant increases in E7-specific CD8~+ T cell responses and impressive antitumor effects against E7-expressing tumors. Furthermore, the NCRT/E7/hsp fusion protein also generates potent antiangiogenic effects. These results indicate that NCRT/E7/hsp fusion protein is a promising therapeutic vaccine for treatment of HPV-associated cancer through a combination of antigen-specific immunotherapy and antiangiogenesis, with possible therapeutic potential in clinical settings.