Anti-tumor Effect Of Immunotherapy With Vaccine Based On The Recombination FGFR1-MIP3α/Fc Fusion Protein In Mice

Objective: Using the previously prepared mouse fibroblast growth factor receptor 1-macrophage inflammatory protein3α-Fc fusion protein(FGFR1-MIP3α/Fc)as a vaccine to observe the anti-tumor effect,and preliminary explore its mechanism of action.Methods: Using the previously successfully prepared FGFR1-MIP3α/Fc fusion protein as a vaccine to observe the anti-tumor effect through tumor volume and survival curve in 4T1 breast cancer mouse models.The number of CD11 c and CD86 double-label positive dendritic cells detected byflow cytometry;The tumor tissue specificity and vascular targeting FGFR1 were identified by anti-FGFR1 immunofluorescence staining;The microvessel density detected by anti-CD31 antibody immunohistochemistry,the tumor cells apoptosis detected by TUNEL assay and proliferation of tumor cells detected by anti-PCNA antibody immunohistochemistry,respectively.Results:(1)The FGFR1-MIP3α/Fc fusion protein vaccine significantly inhibited tumor growth,tumor volume and tumor weight was significantly reduced.(2)The number of dendritic cells(CD11c and CD86 double-labeled)significantly higher in the FGFR1-MIP3α/Fc treatment group(91.27%)than that of FGFR1-Fc group(23.13%),MIP3α-Fc group(71.35%),and control group(33.75%).(3)FGFR1 immunofluorescence revealed that both FGFR1-MIP3α/Fc and FGFR1-Fc treatment groups could specifically recognize microvessels in tumor tissues,and there was no obvious fluorescence signal in other tissues.The control antibody did not stain the tumor microvessels.(4)The microvessel density was significantly lower in the FGFR1-MIP3α/Fc group than in FGFR1-Fc,MIP3α-Fc,and NS control group(11.5±1.51 versus 17.2±1.03,29.5±2.46,43.6±2.29).(5)Tumor cell apoptosis index detected by TUNEL was significantly higher in the FGFR1-MIP3α/Fc group(26.5 ± 2.84)than that of FGFR1-Fc group(17.3±1.25),MIP3α-Fc group(13.9 ± 2.02),and NS control group(8.1 ± 0.94)(P < 0.05 for all).(6)Tumor cell proliferation index detected by anti-PCNA antibody immunohistochemistry was significantly higher in the FGFR1-MIP3α/Fc group than in FGFR1-Fc,MIP3α-Fc,and NS control group(11.6 ± 1.26 versus 16.5 ± 1.43,21.7 ± 1.49,30.8 ± 3.52,P < 0.05).Conclusion:(1)FGFR1-MIP3α/Fc fusion protein vaccine could significantly inhibit the tumors growth.(2)FGFR1-MIP3α/Fc fusion protein could significantly inhibit the tumor angiogenesis related-FGFR1.(3)FGFR1-MIP3α/Fc fusion protein couldinduce dendritic cells chemotaxis to a certain extent.(4)The mechanism of FGFR1-MIP3α/Fc fusion protein suppressed tumor growth may be to the synergistically inhibition of tumor angiogenesis and cell proliferation,promotion of immune effects and tumor cell apoptosis.