Cripto-1 plasmid DNA vaccination targets metastasis and cancer stem cells in murine mammary carcinoma
Menée in vitro et à l'aide de modèles murins de tumeur mammaire, cette étude met en évidence l'intérêt thérapeutique d'un plasmide exprimant Cripto-1, une oncoprotéine fœtale surexprimée dans les cancers invasifs du sein et les cellules souches cancéreuses
Metastatic breast cancer is a fatal disease that responds poorly to treatment. Cancer vaccines targeting antigens expressed by metastatic breast cancer cells and cancer stem cells could function as anticancer therapies. Cripto-1 is an oncofetal protein overexpressed in invasive breast cancer and cancer-initiating cells. In this study, we explored the potential of a Cripto-1-encoding DNA vaccine to target breast cancer in preclinical mouse models. BALB/c mice and BALB-neuT mice were treated with a DNA vaccine encoding mouse Cripto-1 (mCr-1). BALB/c mice were challenged with murine breast cancer 4T1 cells or TUBO spheres; BALB-neuT mice spontaneously developed breast cancer. Tumor growth was followed in all mouse models and lung metastases were evaluated. In vitro assays were performed to identify the immune response elicited by vaccination. Vaccination against mCr-1 reduced primary tumor growth in the 4T1 metastatic breast cancer model and reduced lung metastatic burden. In BALB-neuT mice, because the primary tumors are Cripto-1 negative, vaccination against mCr-1 did not affect primary tumors but did reduce lung metastatic burden. Spheroid cultured TUBO cells, derived from a BALB/neuT primary tumor, develop a cancer stem cell like phenotype and express mCr-1. We observed reduced tumor growth in vaccinated mice after challenge with TUBO spheres. Our data indicate that vaccination against Cripto-1 results in a protective immune response against mCr-1 expressing and metastasizing cells. Targeting Cripto-1 by vaccination has promise as an immunotherapy for treatment of metastatic breast cancer.
Cancer Immunology Research , résumé, 2017