The Development of Human Papillomavirus Type 16 E7-Specific Human Immunologic Assays in Non-HLA2 Type Human Being

Cervical cancer the most frequent neoplasm and the third mortality rate of malignancies of the women in the world. It results in about 200,000 women dying of cervical cancer each year worldwide. The available forms of treatment-surgery, radiation therapy, and chemotherapy are all cytoreductive treatment modalities, so in addition to killing cancerous cells, healthy cells are also destroyed in the process. Indeed, there is a need to decrease the incidence of cervical cancer and develop better forms of its treatment. Human papilloma viruses (HPV) have been consistently implicated in causing cervical cancer especially those high-risk types (HPV 16,18,31,45) have been strongly associated with cervical cancer. HPV 16 was found in more than 50% of cervical cancer tissues. So the host immune response plays an important role in determining the regression of cervical abnormality or persistence and progression to malignancy via targeting HPV. The ideal cancer treatment should be able to eradicate systemic tumors at multiple sites in the body while having the specificity to discriminate between neoplastic and nonneoplastic cells. In this regard, antigen-specific cancer immunotherapy represent an attractive approach for cancer treatment. It is now clear that major histocompatibility complex (MHC) class I restricted CD8+ T cytotoxic cells are critical to the generation of antitumor immunity. Cell-mediated responses are critical in anti-tumor immunity. By cooperating with Dr. TC Wu in Johns Hopkins Medical Institutes, we have recently developed some E7-specific cancer vaccines of different strategies such as DNA, or replication-defective SINrep5 virus. We found that these E7-chimeric DNA vaccines are capable of preventing and treating the growth of murine model tumors expressing E7. These positive results from the preclinical murine models have encouraged us to focus on the development of cancer vaccine and immunotherapy and apply these vaccines to human subjects. However, it is very important to set up various E7-specific immunologic assays of human being to evaluate the effect of cancer vaccine or immunotherapy in the future clinical trials. So we would like to provide this proposal to address on the development of HPV 16 E7-specific immunologic assays in human being.