CD133 mRNA-transfected dendritic cells induce coordinated cytotoxic and helper T cell responses against breast cancer stem cells
| Autor: | Lincoln A. Edwards, John S. Yu, Angelique Sao-Mai Sy Tay, Takayuki Amano |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
T cell Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dendritic cell Biology Major histocompatibility complex Immune system medicine.anatomical_structure breast cancer Oncology Antigen Cancer stem cell embryonic structures Cancer research biology.protein medicine Molecular Medicine Cytotoxic T cell dendritic cell vaccine Pharmacology (medical) Original Article CD133 Stem cell RC254-282 |
| Zdroj: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 22, Iss, Pp 64-71 (2021) |
| ISSN: | 2372-7705 |
| Popis: | 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. Graphical abstract Triple-negative breast cancer stem cells with CD133 expression show increased resistance to current therapies. Tay et al. show that a coordinated cytotoxic and helper T cell response is generated from vaccination with dendritic cells transfected with CD133 mRNA. Mammary tumor growth decreased and survival times increased in a syngeneic breast cancer mouse model. |
| Databáze: | OpenAIRE |
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