Pharmacodynamic Study Of Immunostimulatory Antibody Combined With HPV16 E7 Polypeptide In Cervical Cancer

High-risk human papillomavirus(HPV)-associated infections are the leading cause of vaginal and cervical condyloma and eventually lead to cervical cancer.HPV infection has become a major health concern worldwide.At present,treatment most widely used in clinical,are to remove steroids,with or without non-specific immunotherapy methods,which may have certain curative effects in a short period of time,but can not completely eliminate the virus in the cells,and can not effectively control the recurrence of the disease.In order to make up for the shortcomings of current treatment methods,therapeutic vaccines have become a hot spot for therapy of anti-HPV and related tumors research,but their individual effects are not good enough.Previous studies have shown that cytotoxic T lymphocytes(cytotoxic T lymphocytes,CTLs)mediated specific cellular immunity plays an important role in anti-tumor reaction.Therefore,effectively eliciting a specific CTL response become an important target of therapeutic vaccines.With the progressment of immunological checkpoint research,combination with monoclonal antibody agonists of tumor necrosis factor receptor(TNFR)family members,has become a new therapeutic strategy.Experimental method: Firstly,the study will inoculate mice with congenital immune stimulator and HPV16 E7 polypeptide,as well as the immunostimulatory antibody CD40 independently developed by our laboratory.Subsequently,cervical cancer TC-1 tumor cells were implanted subcutaneously in mice to evaluate their ability to prevent cervical cancer.Subsequently,this study established a mouse cervical cancer TC-1 tumor model,and the laboratory’s self-developed immunostimulatory antibody combined with HPV16 E7 polypeptide and innate immune stimulant to observe its effect on cervical cancer.The changes of immunological indexes in experimental animals were detected by flow cytometry,and the changes of biomarkers were obtained.The results of this study: In the experiment of preventing tumors,there was no significant difference in the growth trend between the treatment group and the blank control group(P>0.05),but the combined group showed a slower trend of tumor growth compared with the blank control group;The immunological indicators of the drug group also showed an increasing trend of antigen-specific T cells.In the tumor treatment experiment,the combined immunostimulatory antibody 4-1BB can significantly inhibit the growth of tumor;the proportion of antigen-specific T cells in immunological indicators increased,and statistically significant(P<0.05),the proportion of regulatory T cells was decrease,and it was statistically significant(P<0.05).The combination of immunostimulatory antibody 4-1BB and CD40 also significantly inhibited tumor growth,and the proportion of antigen-specific T cells in immunological indicators increased significantly(P < 0.001).Above all,we conclusion that: combined administration can significantly inhibit tumor growth;increase the survival rate of tumor models and prolong the survival time of tumor model animals,among them,the effect of immunostimulatory antibody 4-1BB is particularly prominent..The results of immunological cells variation showed that the combined administration can significantly enhance the immune response,and exert anti-tumor effects by promoting the proliferation and activation of lymphocytes,especially the activation of antigen-specific CTL.This study indicate that the combination of native and adapt immunazition is effective,and could provide new strategy for the treatment of cervical cancer,however,the specific mechanism and mechanism need to be investigated further,for better efficacy.