Cervical Cancer Nanoparticle Vaccine With HSP110 As Adjuvant Can Effectively Prolong The Survival Rate Of Tumor-bearing Mice

Objective:We aimed to design a novel self-assembled nanoparticle HPV16vaccine through combining RGD-GGG-K18 and fusion double expression plasmid pIRES2-3×E7-HSP110-EGFP,and discuss how it increases the immune response and the therapeutic effect ex vivo and in vivo.Methods:Nanoparticles were prepared and identified by Gel retardation,TEM and DNase I protection assays.Flow cytometry,ex vivo specific cytolysis of CTL-lactate dehydrogenase release analyzed the vaccine-induced immune responses.The tumor protective effectiveness of nanoparticle RGD-GGG-K₁₈/pIRES2-3×E7-HSP110-EGFP was investigated in the prophylactic and therapeutic mice models in vivo.Results:This type of vaccine formed the around 50nm nanoparticles.The results of immunofluorescence and competitive inhibition test showed that the way of AK targeting tumor cells in vitro was mainly through the specific combination of RGD peptide and?_v?₃.It was found that the nanoparticles could transfer the exogenous gene into mammalian cells.And it greatly improved epitope-specific immune response both ex vivo and in vivo.More importantly,this vaccine type could decrease tumor growth and improve long-term survival in animals.Improved frequency of E7-specific CD8⁺memory T cells could be the underlying mechanisms.Conclusions:These results suggest the nanoparticle RGD-GGG-K₁₈/pIRES2-3×E7-HSP110-EGFP not only provide a new form of cervical cancer vaccine,lay the foundation for further development potential of HPV immunotherapy;but also through the study of the vaccine immune effect and mechanism,to provide new ideas and experimental technique of specific prevention and treatment for other cancers,it has broad potential application value.