CD133 mRNA-transfected dendritic cells induce coordinated cytotoxic and helper T cell responses against breast cancer stem cells

• Main Authors: Angelique Sao-Mai Sy Tay, Takayuki Amano, Lincoln A. Edwards, John S. Yu
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Series: Molecular Therapy: Oncolytics
• Subjects: CD133; breast cancer; dendritic cell vaccine
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770521000723

Breast cancer, a leading cause of death yearly, has been shown to be initiated and propagated by cancer stem cells. CD133, a cell surface antigen, has been shown to be present on cancer stem cells of many solid tumors, including breast cancer. A limitation to targeting CD133 is major histocompatibility complex (MHC)-restricted presentation of epitopes, leading to activation of only one arm of the immune system: either CD4+ helper T cells or CD8+ cytotoxic T cells. Thus, we hypothesized that by creating an MHC-independent vaccination, we would give rise to a sustained immune response against CD133 in triple-negative breast cancer (TNBCs). We transfected CD133 mRNA into dendritic cells and then tested this in animal models of TNBC. We showed in these models the activation of both CD8+ cytotoxic T cells and CD4+ helper T cells by dendritic cell vaccination with modified CD133 mRNA, with subsequent decrease in tumor growth. This study for the first time demonstrates in a syngeneic mouse model of TNBC that targeting CD133, in an MHC-independent manner, is an effective strategy against the cancer stem cell population, leading to tumor abrogation.