α-fetoprotein - specific tumor immynity induced by plasmid DNA vaccination

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DNA vaccination using the tumor specific antigen gene is a promising strategy for cancer immunotherapy. In the present study, we examined whether the vaccination with plasmid DNA expressing a -fetoprotein (AFP) gene could inhibit the growth of mouse hepatoma cells since AFP is specifically expressed in hepatoma cells and used clinically as a tumor marker of hepatoma. We have constructed the mouse AFP expressing plasmid vector, pCMAFP, and adenovirus vector, AdAFP, respectively. The transduction of these mouse AFP expressing vehicles into HeLa cells resulted in the adequate expression of mouse AFP although AdAFP showed much better expression than pCMAFP. To examine the inhibitory effect of pCMAFP vaccination on the growth of mouse hepatoma cells, mice were immunized by the subcutaneous injection with 100 μg of pCMAFP. Two weeks later, 5 x 10^6 of MH134 mouse hepatoma cells were inoculated into back subcutaneous of each mouse, and the tumor growth was measured. pCMAFP vaccination alone showed only a slight inhibition of tumor growth, however, co-introduction of plasmids expressing hematopoietic growth factor genes such as GMCSF and MCSF with PCMAFP effectively inhibited the tumor growth. More over, a booster vaccination with 10^9 PFU of AdAFP one week after first vaccination also showed the apparent inhibition of tumor growth. We performed the similar experiments using another mouse hepatoma cells, Hepal-6, which produce AFP more abundantly than MH134. The growth of Hepl-6 was more effectively inhibited by PCMAFP vaccination than that of MH134, which may be relevant to the differences of AFP productivity in these cells. These results suggest that AFP DNA vaccination may have a therapeutic potential in the treatment of hepatoma.