Induction of Cytotoxic T Lymphocyte Response against the E6 Oncogene of Human Papillomavirus Type 16 in C3H/HeJ Mice
Human papiilomavirus (HPV) type 16 has been identified in the majority of invasive carcinomas of the uterine cervix and found to contribute significantly to the genesis of human genital cancer. Cervical cancer associated with HPV has been used as a model system for the development of cancer immunotherapy. Here we show that cell lines infected with retrovirus containing HPV-16 E6 gene can induce a specific CTL response in C3H/HeJ mice. We have cloned E6 cDNA of HPV-16 in retroviral expression vectors, and introduced them into mouse Ltk and NCTC2555 cell lines originated from C3H/He mice. When C3H/HeJ mice were immunized with the transfected cell lines, specific CTL responses were induced. However, the CTL response was not induced with nontransfected cells. In addition, we have shown that different clones of transfectants resulted in different levels of specific killing when they were used as targets, probably due to different levels of E6 gene expression. These results suggest a possibility that E6 DNA can be used to induce CTL acitivity against the antigen in mice and can be further developed as a therapeutic and preventive DNA vaccine. They also suggest that an efficient immunotherapy requires not only a potent immunogen but also a high level expression of a surface target antigen.
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