Development of Therapeutic Cancer Vaccine

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ABSTRACT (no more than 30 lines of text) HER2-positive breast cancer accounts for 20-30% of all breast cancer incidences. Although there are small molecule inhibitors targeting the HER2 receptor tyrosine kinase and therapeutic antibodies specific for the HER2 protein, tens of thousands of patients still die of late-stage HER2-positive breast cancer every year. In the pursuit for novel and effective treatments, we recently developed a therapeutic cancer vaccine for HER2-positive breast cancer. This vaccine is composed of HER2-specific antigen peptides and soluble adjuvants that are loaded into the nanopores of a porous particulate adjuvant. The final therapeutic vaccine product has a number of unique properties that makes it highly effective including, but not limited to, maintenance of vaccine particle integrity for coordinated functions, preferential uptake and transport by dendritic cells, synergistical stimulation of dendritic cells by promoting secretion of type I interferons and TNF-a, and long-term vaccine activity as a result of sustained release of antigen peptides and soluble adjuvants. Our preliminary studies with murine HER2-positive tumors have revealed that vaccine treatment can stimulate proliferation of HER2 antigen-specific CD8+ T cells and infiltration of T cells into the tumor bed, leading to inhibition of both primary and metastatic tumors. In addition, vaccination does not cause detectable adverse side effects, making it an excellent candidate drug. In this STTR phase I project, we propose studies to further understand the mechanism of action from the therapeutic cancer vaccine and to establish human disease relevance. In the Aim 1 study, we will test the hypothesis that conventional dendritic cells are essential for anti-tumor activity from the vaccine. In the Aim 2 study, we will test the hypothesis that anti-tumor activities observed in murine tumor models can be replicated in humanized mice bearing human HER2-positive cancers. During the course of the study, we will also establish a set of assays for quality control and quality assurance. Upon completion of these studies, we will submit a phase II proposal to support investigational new drug (IND)-enabling studies in preparation for human clinical trials.