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.