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

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-gamma-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-gamma-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-gamma spots/10(6) cells vs 23.60+/-11.80 IFN-gamma spots/10(6) cells, 7.17+/-4.24 IFN-gamma spots/10(6) cells, P<0.01; 126.50+/-8.22 microg/mL vs 51.72+/-3.40 microg/mL, 5.83+/-3.79 microg/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(3), 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.