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Combination therapy of 5-FU and α-galactosylceramide enhances the anti-tumor effect in CT26 cancer model
- Author(s)
- 김민경
- Alternative Author(s)
- Min gyeong Kim
- Advisor
- Haeyoung Suh-Kim
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2023-08
- Language
- eng
- Keyword
- 5-Fluorocytosine; Mesenchymal stem cell; cytosine deaminase; immunotherapy; α-galactosylceramide
- Alternative Abstract
- Cancer immunotherapy has emerged as a promising approach for treating various malignant tumors. In this study, we performed a screening for the most effective PAMP molecule when combined with mesenchymal stem cells expressing cytosine deaminase (MSC/CD) and 5-fluorocytosine (5-FC) in a colon cancer model, resulting in the identification of α-galactosylceramide (α-GalCer). In addition, we determined the optimal timing and frequency of administration for maximized therapeutic effects when used in combination therapy. Our findings demonstrate that the combination of MSC/CD, 5-FC, and α-GalCer induces enhanced antitumor activity compared to individual treatments. This enhancement is primarily due to the increased immune response incited by the administration of α-GalCer. In particular, intratumoral injection of α-GalCer increases natural killer T (NKT) cell infiltration and activation into the tumor microenvironment. These findings lead to the infiltration and activation of immune cells within the tumor microenvironment, including natural killer (NK) cells, T cells, and antigen presenting cells (APCs) such as dendritic cells (DCs) and M1 macrophages. In addition, proinflammatory and chemokine levels in tumors increase due to the activation of immune cells. IFN-γ functions as a key central cytokine, and tumor cell death is increased through increased Granzyme B with 5-FU. <br> Therefore, the combined administration of MSC/CD, 5-FC, and α-GalCer effectively enhances both innate and adaptive immune responses, thereby amplifying anticancer efficacy. <br> We also observed no hepatotoxicity induced by α-GalCer. The systemic inflammation and increase in anti-inflammatory cytokines were found to be transient reactions, indicating the safety of our combined approach in the context of immunotherapy. <br> Our research underscores the potential therapeutic benefits of integrating MSC/CD, 5-FC, and α-GalCer for colon cancer treatment, and contributes valuable insights to the field of cancer immunotherapy. Future studies should be focused on elucidating the fundamental mechanisms and exploring the possibility of applying these findings to other types of cancer and immune therapeutic strategies.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 4. Theses(Ph.D)
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