This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Cancer vaccine clinical trials performed over the last few years have demonstrated that patients can be immunized against specific tumor antigens. Cancer, however, is not caused by a single genetic alteration but rather by multiple genetic alterations and the function of multiple aberrant proteins. A problem facing tumor immunologists today is how to vaccinate cancer patients against multiple antigens involved in the malignant transformation. DNA based immunization offers a technology that is easily adapted to the delivery of multiple antigens driving the malignant process. Immunization with plasmid DNA, however, has not resulted in the reproducible generation of systemic immunity in a variety of models of infectious disease antigens. We hypothesize it will be possible to improve the efficacy of in vivo antigen presenting cells (APC) transfection with DNA vaccines by the use of local soluble cytokines such as GM-CSF.
The specific aims of this proposal are to (1) determine the safety of HER2 ICD plasmid based DNA vaccination in patients with advanced stage HER2 overexpressing breast and ovarian cancer, (2) determine the immunogenicity of HER2 ICD plasmid based DNA vaccination focusing on T cell response, (3) determine if the dose of HER2 ICD plasmid based DNA vaccination effects the development of an immune response, and (4) determine whether intra and intermolecular epitope spreading occurs with HER2 ICD DNA immunization. The long-term goal will be to use this study as a platform to develop multi-antigen plasmid based vaccines for the prevention of common solid tumors.
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