|The Cervical Cancer Research Lab of|
Drs. T.-C. Wu & Chien-Fu Hung
We are currently developing vaccines and immunotherapeutic strategies for the prevention and treatment of human papillomavirus (HPV)-associated cervical cancer.
Each year, approximately 500,000 women worldwide develop cervical cancer and about 200,000 of these women die. A worldwide study showed HPV DNA existed in more than 99% of cervical cancer specimens taken from women with cervical cancer. A large portion of cervical cancer is particularly associated with HPV types 16 and 18. The viral proteins E6 and E7 play a role in the transformation of HPV-infected cells to tumor cells. These proteins are consistently expressed in cervical cancer cell lines and HPV-associated neoplasms. Thus, E6 and E7 represent true tumor-specific antigens and allow for the development of immunotherapeutic strategies to combat HPV-associated cancers. Because HPV E7 is highly immunogenic, cellular immune responses specific for this tumor antigen are generally higher than E6. Therefore, the development of new vaccines focus on inducing high E7-specific cytotoxic T cell responses. A novel form of vaccine, the DNA vaccine, was developed only a few years ago. This vaccine consists of a specific gene of interest that is injected into muscle or skin, i.e. HPV-16 E7. The expression of E7 DNA in antigen-presenting cells can induce an effective cellular immune response specific to the E7 antigen.
The activity of antigen-specific T cells is known to be crucial in combating cancer. To enhance T cell-mediated immunity, we have focused on enhancing antigen processing and presentation by dendritic cells using intracellular targeting and intercellular spreading strategies. Intracellular targeting directs antigen to different subcellular locations to enhance the quality of antigen processing and presentation. Meanwhile, intercellular spreading facilitates the spread of antigen to neighboring cells by taking advantage of unique membrane translocation properties, allowing for an increase in the amount of antigen presented to effector cells. The continued development of these strategies will facilitate the development of ideal vaccines that generate a potent immune response and antitumor effect against cancer. We are also actively involved with investigating mechanisms of tumor evasion, identifying new tumor-specific antigens, and applying our vaccine strategies to other cancer systems with tumor-specific antigens (i.e. breast cancer, ovarian cancer, etc.).
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