Poliovirus Tumor Vaccine for Breast Cancer Micro-Metastases

摘要

The underlying reason for failure to cure patients diagnosed with breast cancer is the presence of micrometastases. The stimulation of anti-tumor immune responses represents one of the more effective ways to treat low tumor burdens that are clinically occult. The objective of our proposal is to determine whether a poliovirus replicon vaccine strategy induces systemic immunity an eradication of micrometastases. During our project, we have constructed and characterized poliovirus replicons which express CE or HER2/neu. Mice given these replicons generate anti-CEA or HER2/neu antibodies. We had demonstrated protection from tumor challenge in the mice which have antibodies to CEA. The significance of these studies is that we have now characterized the appropriate replicons that will be used to establish route of administration for generating an immune response against CEA or HER2/neu prior to tumor challenge. We developed companion replicons which express biological active immune modulators (GMCSF and IL-2) to increase the immunogenicity of the replicon encoding CEA or HER2/neu. Characterization of the immune response to antigens in mice revealed typical TH1 response. The results of our studies provide the foundation for future strategies to us replicons as anti-tumor vaccines.