Antitumor immunity induced by DNA vaccine encoding alpha-fetoprotein/heat shock protein 70

摘要

AIM: To construct a DNA vaccine encoding human alpha-fetoprotein (hAFP)/heat shock protein 70 (HSP70), and to study its ability to induce specific CTL response and its protective effect against AFP-expressing tumor. METHODS: A DNA vaccine was constructed by combining hAFP gene with HSP70 gene. SP2/0 cells were stably transfected with pBBS212-hAFP and pBBS212-hAFP/HSP70 eukaryotic expression vectors. Mice were primed and boosted with DNA vaccine hAFP/HSP70 by intramuscular injection, whereas plasmid with hAFP or HSP70 was used as controls. ELISPOT and ELISA were used to detect IFN-γ-producing splenocytes and the level of serum anti-AFP antibody from immunized mice respectively. In vivo tumor challenge was measured to assess the immune effect of the DNA vaccine. RESULTS: By DNA vaccine immunization, the results of ELISPOT and ELISA showed that the number of IFN-γ-producing splenocytes and the level of serum anti-AFP antibody were significantly higher in rhAFP/HSP70 group than in hAFP and empty plasmid groups (95. 50+-10. 90 IFN-γ spots/10~6 cells vs 23.60+-11.80 IFN-y spots/10~6 cells, 7.17+-4.24 IFN-γ spots/10~6 cells, P < 0.01; 126.50+-8.22 μg/mL vs 51.72+-3.40 μg/mL, 5.83+-3.79 μg/mL, P < 0.01). The tumor volume in rhAFP/HSP70 group was significantly smaller than that in pBBS212-hAFP and empty plasmid groups (37.41+-7.34 mm~3 vs-381.13+-15.48 mm~3, 817.51+-16.25 mm, P < 0.01). CONCLUSION: Sequential immunization with a recombinant DNA vaccine encoding AFP and heat shock protein70 could generate effective AFP-specific T cell responses and induce definite antitumor effects on AFP-producing tumors, which may be suitable for some clinical testing as a vaccine for HCC.