CD4+ T Cell Epitope-based Heterologous Prime-boost Vaccination As A Novel Strategy Against Tumor

Tumor has long been one of the biggest threats to human beings because of its high morbidity and mortality,and the curative effects of conventional treatment,such as surgery,radiation or chemotherapy,seem to be unsatisfying.However,the promising results from clinical trials of immunotherapy shift people's attention to those methods harnessing a patient's own immune system to defeat tumor,among which tumor vaccines represent a viable option.In our research,we inoculate the mice with the tumor cell line(B16-gp),which was established by inserting LCMV specific glycoprotein(gp)as a surrogate neoantigen into B16 melanoma tumor cells.Those tumor bearing mice were then primed by a Listeria monocytogenes vector expressing I-A~b restricted CD4+T cell epitope GP61-80(Listeria-gp61)firstly and then boosted by an influenza A virus(PR8 strain)vector that carries the same epitope(IAV-gp61).We observed that this vaccination strategy could not only be prophylactic but also have remarkable therapeutic effects towards established tumors,because immunized mice showed significantly slower tumor progression,delayed tumor metastasis,longer survival duration,enhanced survival rate and reduced severity of relapses.Through flow cytometry analysis,we found that the prime-boost vaccination strategy improved both the quantity and quality of tumor infiltrating T cells as well as T cells in the spleen and draining lymph nodes,which gave rise to a better control of tumor.The efficacy could be further improved when combined with anti-PD-L1 treatment.Therefore,the CD4+T cell epitope-based heterologous prime-boost immunization and strategically combining other agents or approaches that synergistically enhances antitumor efficacy,may pave the way for designing optimal vaccine regimen with improved clinical outcomes in cancer patients.