DNA vaccine against oncogenic hamster cells transformed by HPV16 E6/E7 oncogenes and the activated ras oncogene

The capability of DNA to elicit anti-tumour immunity was studied using huma n papillomavirus type 16 (HPV16)-transformed Syrian hamster cells denoted K 3/II. These cells had been derived after cotransfection of primary kidney c ell cultures with p16HHMo plasmid containing E6/E7 oncogenes of HPV 16 and pEJ6.6 plasmid containing the activated human H-ras oncogene; they express both the HPV16 and activated H-rns genes. As a DNA vaccine, the p16HHMo pla smid was used. Three doses of the plasmid (either 100 mu g or 10-15 mu g pe r dose) were administered intramuscularly at 3-week intervals. The animals were challenged with four different doses (10(3)-10(6) per animal) of K3/II cells 18 days after the last plasmid injection. In one experiment the lowe r dose of plasmid DNA was also given in a mixture with the cationic lipid D OTAP. In another experiment, the pEJ6.6 plasmid (100 mu g per dose) was use d either alone or in combination with plGHHMo. In all experiments animals i noculated with the same doses of pBR322 plasmid served as controls. A moder ate protective effect was observed in animals inoculated with the 100-mu g doses of plGHHMo, but not in those inoculated with 10-15 mu g of the same p lasmid, whether given with or without DOTAP. A protective effect was also o bserved after administration of the pEJ6.6 plasmid. At the time of challeng e a portion of the p16JJMo-immunized, but not the pBR322-treated, animals p ossessed antibodies reactive in ELISA with peptides derived from the N-term inal portion of HPV 16 E7 protein and with one peptide derived from E6 prot ein, while two other E6 peptides exhibited non-specific reactivity.