A major clinical problem in the treatment of patients with advanced stage breast and ovarian cancer is the risk of relapse. The majority of patients diagnosed with high risk or more advanced stage cancers, although rendered disease free with standard treatments such as surgery and chemotherapy will undergo disease reoccurrence. Cancer vaccines offer a unique therapeutic strategy that may prevent cancer relapse or even eradicate micrometastatic disease. Several advances in tumor immunology in the last decade have resulted in renewed interest in cancer vaccines; the definition of specific tumor antigens, the understanding that cancers such as breast and ovarian are immunogenic, and the development of techniques that can result in immunizing patients effectively to """"""""self"""""""" tumor antigens. Our group has been developing plasmid based DNA vaccines as a method that may be effective in immunizing patients against multiple antigens expressed in their tumors. Delivering tumor antigen encoding plasmids interdermally with soluble cytokines that enhance local skin dendritic cell recruitment, thus, markedly improving the immunogenicity of the approach has resulted in the development of a Phase I clinical study of a plasmid based vaccine targeting the HER-2/neu (HER2) oncogenic protein in patients with HER2 overexpressing breast and ovarian cancers. The clinical study is designed to determine the safety and immunogenicity of DNA immunization. Experiments outlined in this proposal will determine whether immunologic memory against the HER2 antigen can be generated after active immunization. Several clinical trials of cancer vaccines have demonstrated that cancer patients can be immunized to develop detectable immunity. My goal will be whether immunization has resulted in the development of a T cell memory response directed against tumor specific proteins. Theoretically an effective cancer vaccine will result in the generation of immunologic memory and this memory T cell response, if effective, would potentially be able to prevent disease relapse.
The specific aims of this proposal are to: (1) evaluate the safety and measure the extent of immunogenicity of HER2 ICD plasmid based DNA vaccination in patients with advanced stage HER2 overexpressing breast and ovarian cancer, (2) determine whether HER2 specific T cell memory occurs after active immunization with a HER2 ICD plasmid based vaccine, and (3) determine if prolonged local antigen expression is associated with the development of HER2 specific memory T cell response after immunization. ? ? ?
|Disis, Mary L; Wallace, Danelle R; Gooley, Theodore A et al. (2009) Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J Clin Oncol 27:4685-92|
|Salazar, Lupe G; Coveler, Andrew L; Swensen, Ron E et al. (2007) Kinetics of tumor-specific T-cell response development after active immunization in patients with HER-2/neu overexpressing cancers. Clin Immunol 125:275-80|