Effective immunotherapy of cancer by DNA vaccination

Direct injection of naked plasmid DNA either intramuscularly or intradermal ly induces strong, long-lived cell-mediated and humoral immune responses to the antigen encoded by the gene vaccine, In the present study, we used gen e vaccination with naked plasmid DNA to induce prophylactic immune response s to tumor associated antigens. MAGE-1 (melanoma antigen 1) is an ideal can didate for cancer vaccines because it belongs to a family of genes that are expressed in a number of human tumors of various histological types but no t in normal adult tissues except for the testis, and because both humoral a nd cell-mediated immune responses against MAGE-1 antigen were detected in t umor patients. Intradermal administration of plasmid DNA encoding MAGE-1 (p chMAGE1) induced anti-MAGE-1-specific antibody in BALB/c mice, In contrast, no detectable level of anti-MAGE-1 antibody was induced by intramuscular i njection of pcMAGE1. Also, intradermal injection of pcMAGE1 was capable of generating CTLs reactive with MAGE-1-transfected murine tumor cells, M-MSV- MAGE1, Most of the mice (8 out of 10) immunized with pcMAGE1 rejected the c hallenge of M-MSV-MAGE1 tumor cells, compared with control animals most of which developed tumors. This suggests that intradermal DNA vaccination coul d provide a novel immunotherapy of cancer.