Abstract A77: Cripto-1 vaccination elicits protective immune response to metastatic breast cancer and breast cancer stem cells

Metastatic breast cancer is a fatal disease responding poorly to classical treatments. Cancer vaccines targeting antigens expressed by metastatic breast cancer and cancer stem cells (CSC) have the potential to become potent anti-cancer therapies. Cripto-1 is an onco-fetal protein frequently overexpressed in invasive breast cancer and cancer-initiating cells. It is involved in cellular processes such as cell migration, epithelial-mesenchymal transition, and invasion, hallmarks of aggressive cancers. In this study we explored the potential of a Cripto-1 encoding DNA vaccination to target metastatic breast cancer and breast cancer stem cells in preclinical models. Mice were vaccinated with a DNA vaccine encoding for mouse Cripto-1 (mCR) prior tumor challenge. In the 4T1 metastatic breast cancer model vaccination against mCR resulted in reduced primary tumor growth and significantly reduced metastatic burden in the lung. We further identified Cripto-1 specific antibodies in this model generated by the vaccination. TUBO is a Cripto-1 negative breast cancer cell line and vaccination against mCR in the transplantable BALB/c TUBO model did not result in protection. We show that spheroid culture of TUBO results in up-regulation of Cripto-1 on the cell surface. In addition, TUBO spheres display cancer stem cell phenotype. Consequently, tumor progression was inhibited in anti-mCR vaccinated mice challenged with TUBO spheres but not in control vaccinated mice. Our data indicates that DNA vaccination against Cripto-1 results in a protective immune response against mCR expressing tumors. Targeting Cripto-1 by vaccination is a promising potential immunotherapy for treatment of metastatic breast cancer. Citation Format: Kristina Witt, Maarten Alexander Ligtenberg, Laura Conti, Stefania Lanzardo, Roberto Ruiu, Helena Tufvesson-Stiller, Jeanette Ostling, Charlotte Rolny, Alvaro Lladser, Andreas Lundqvist, Federica Cavallo, Rolf Kiessling. Cripto-1 vaccination elicits protective immune response to metastatic breast cancer and breast cancer stem cells [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A77.