B7-1 Costimulating Gene Immunization Potentiates Human Papillomavirus Type 16 E6E7 DNA Vaccine-induced Antitumor Immune Response

Human papillomaviruses (HPVs),which are important infectious agents,play a role in induction of proliferative or even malignant changes of human epidermis and mucosa. According to their relation to benign or malignant neoplasia respectively, they are divided into "low risk"and"high risk" groups. HPV type 16, the most important member in"high risk"groups , contributes to the development of cervical carcinomas and other kind of cancer such as oral squamous epithelium cancer, lung cancer and so on. Previous studies have unambiguously shown that HPV16 E6 and E7 are major transformational genes and consistently and exclusively express in HPV16-induced cancer and play major role in the development and maintenance of the malignant phenotype. The data from epidemiological investigation also showed that HPV16 E6 and E7 oncoproteins were able to elicit immune responses in infected population, therefore, E6 and E7 are good examples of a tumor-associated antigens that are suitable for preparation of prophylactic or therapeutic vaccine against the tumors.Because of the safety concerns, the direct use of an unmodified oncogene is impossible in human DNA vaccination. Data demonstrated that point mutation at the 24^th amino acid at the Rb binding site of E7 could eliminate its transformation potential. In order to cover more antigen epitopes, we used the fused E6E7 genes of HPV16 which from DNA of a Chinese patient with cervical cancer in Shandong province as target gene of DNA vaccine to study its immunologic potential. The defined mutation by site-directed mutagenesis was introduced at the 24^th amino acid of E7 to inactivate the Rb binding site, then the termination coden of E6 was altered by a site-directed mutagenesis to create an E6E7...