Application Of Cell-Penetrating Peptide In Cancer Immunotherapy

The development of effective cancer vaccines is an important direction in the area of cancer immunotherapy.Although certain types of preventive cancer vaccines have already been used in clinic,therapeutic cancer vaccines for treatment of already-established tumors are still highly demanded.In this study,we develop a new type of cancer vaccines by mixing cell-penetrating peptide(CPP)conjugated antigen as the enhanced antigen,together with CpG as the immune adjuvant.A special CPP,cytosol-localizing internalization peptide 6(CLIP6),which has the ability to enter cells exclusively via a non-endosomal mechanism,i.e.direct translocation across the cell membrane,is conjugated with model antigen ovalbumin(OVA).Based on the above information,the first chapter briefly introduce cancer immunotherapy,cancer vaccines,antigen cross-presentation,cell-penetrating peptides.Then,the following work is conducted:The second chapter described the CLIP6-based cancer vaccine strategy and optimized the conjugation between OVA and CLIP6.The conjugation molar ratio of OVA to CLIP6 was determined by fluorescent quantitation with an average of 1:8.The obtained conjugate shows greatly increased uptake by dendritic cells(DCs),and more importantly,the internalization mechanism of CLIP6-OVA is non-endosomal mechanism.In the third chapter of this thesis,CLIP6-OVA remarkably enhanced antigen cross-presentation with the help of CpG This CLIP6-OVA/CpG formulation could act as a preventive vaccine to offer effective protection for mice against challenged B 16-OVA tumors,and is able to further function as a therapeutic vaccine,which,in combination with immune checkpoint blockade therapy,can significantly suppress the already-established tumors.Such CLIP6-based cancer vaccine developing strategy shows promising potential towards clinical practice owing to its features in easy preparation,low cost,and remarkable biocompatibility.