Abstract 2369: Molecular profile of a GM-CSF overexpressing breast cancer whole-cell vaccine with systemic anti-tumor activity

BACKGROUND AND PURPOSE OF STUDY: The allogeneic whole-cell cancer vaccine BriaVax(TM) (formerly SV-BR-1-GM) is an ER/PR negative, HER2/neu positive breast cancer cell line (SV-BR-1) we engineered to stably overexpress GM-CSF. BriaVax, rendered proliferation incompetent by irradiation, has thus far been applied to 4 advanced stage cancer patients (3 subjects with breast cancer, 1 subject with ovarian cancer). One breast cancer subject responded to BriaVax with complete remission of a measurable lung lesion and near complete remission of multiple breast lesions after only 3 inoculations. Nevertheless, she relapsed 3 months after completing the protocol, with brain metastases as well as multiple breast lesions. We obtained FDA permission to resume vaccinations, and, upon doing so, all metastatic sites responded with a prompt tumor regression after only 3 inoculations. To prospectively identify patients with a high likelihood of benefiting from BriaVax therapy we began a program to identify molecular factors of diagnostic potential. Here, we describe a gene expression signature that might both be informative about BriaVax’ mechanism of action and helpful for developing diagnostic or monitoring biomarkers. METHODS: To prospectively identify patients with tumors responsive to BriaVax we began a molecular analysis of both the BriaVax cell line and cells obtained from the special clinical responder's blood. BriaVax gene expression profiles were obtained through Illumina BeadArray and NanoString nCounter technologies and compared to gene expression data sets publically available through the Gene Expression Omnibus (GEO; National Center for Biotechnology Information) portal. RESULTS: BriaVax expresses a gene signature consistent with a mechanism of action involving not only the activation of cytotoxic T cells but also the induction of a humoral response. In addition, BriaVax expresses known cancer antigens. Notably, blood-derived cells of the special clinical responder expressed genes complementing BriaVax’ gene expression signature, thus possibly explaining the unusually prompt and robust clinical response to BriaVax. CONCLUSIONS: Our findings suggest that BriaVax exerts its therapeutic effects via multiple modes. We identified both candidate immunogens overexpressed in BriaVax compared to normal breast cells and unraveled a potential mechanism of action explaining the encouraging clinical response observed. Citation Format: Markus Daniel Lacher, Charles L. Wiseman