Combinational Therapy Using Nanoadjuvantsas Carriers of HPV۱۶ E۷ Epitope Against CervicalCancer

Background: Human papillomavirus (HPV)-induced cervicalcancer is a major health concern in women and therapeuticvaccines can overcome the challenge. Although peptide-basedvaccines are a promising strategy for developing therapeuticvaccines, insufficiency to generate robust immunity limits theirapplication. In the current study, we coated the surface of negatively-charged nanoadjuvants, adenovirus (Ad) and aluminumphosphate (AlPO۴ or Alum), with positively-charged HPV۱۶E۷ epitope to develop an effective combinational regimen withtherapeutic effects on a TC-۱ mouse model.Materials and Methods: To develop an optimal Ad/peptide(Ad/pep) construct, Ads and positively-charged epitopes weremixed at ۱:۱۰۰, ۱:۲۵۰, and ۱:۵۰۰ ratios and their surface chargeand particle size were characterized by zeta potential and dynamiclight scattering. Alum/peptide (Alum/pep) constructsalso were developed by simple mixing of ۲۰ μg of AlPO۴ and۲۰ μg of HPV۱۶ E۷ epitope. The developed constructs wereadministrated into the TC-۱ mouse model according to variousprime-boost vaccination regimens, and finally the levels ofIFN-γ, IL-۱۰, and CTL responses as well as inhibition of tumorgrowth, were measured.Results: Incubation of positively-charged HPV۱۶ E۷ epitopewith Ad and Alum changed the negative charge of nanoadjuvantsto a positive one, without significant changes in their size,indicating that E۷ epitope coated on the surface of nanoadjuvants.Compared with naked nanoadjuvants, homologous administrationof E۷-coated nanoadjuvants exhibited significantanti-tumor activities. Furthermore, we indicated that heterologousregimens, using Ad/Pep-Alum/Pep and Alum/Pep-Ad/Pep, showed superior anti-tumor activities, characterized byhigher levels of IFN-γ, IL-۱۰, and CTL responses, as well asinhibition of TC-۱ tumors in vivo.Conclusion: We introduced a versatile and rapid immunotherapyplatform based on nanoadjuvants and their combinationalregimens that elicits potent anti-tumor immune responses, withoutany genetic engineering processes.

کلیدواژه ها:

Papillomavirus ، Cancer ، Nanoadjuvant ، Adenovirus ، Alum