2. Academic Validation
  3. Holothurian triterpene glycoside cucumarioside A2-2 induces macrophages activation and polarization in cancer immunotherapy

Holothurian triterpene glycoside cucumarioside A2-2 induces macrophages activation and polarization in cancer immunotherapy

  • Cancer Cell Int. 2023 Nov 24;23(1):292. doi: 10.1186/s12935-023-03141-z.
Wen-Han Chuang # 1 2,  Evgeny Pislyagin # 3,  Liang-Yu Lin 1,  Ekaterina Menchinskaya 3,  Oleg Chernikov 3,  Valery Kozhemyako 4,  Tatiana Gorpenchenko 5,  Igor Manzhulo 6,  Elena Chaikina 3,  Irina Agafonova 3,  Alexandra Silchenko 3,  Sergey Avilov 3,  Valentin Stonik 3,  Shey-Cherng Tzou 1 2,  Dmitry Aminin 7 8,  Yun-Ming Wang 9 10
Affiliations

Affiliations

  • 1 Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan.
  • 2 Center for Intelligent Drug Systems and Smart Bio-devices (IDS²B), National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan.
  • 3 Far Eastern Branch, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Russian Academy of Science, 159, Pr. 100 let Vladivostoku, Vladivostok, 690022, Russia.
  • 4 Pacific State Medical University, Ostryakova Avenue, Building 2, Vladivostok, 690002, Russia.
  • 5 Federal Scientific Center of East Asia Terrestrial Biodiversity, Far Eastern Branch of the Russian Academy of Science, 159, Pr. 100 let Vladivostoku, Vladivostok, 690022, Russia.
  • 6 A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch of the Russian Academy of Science, Palchevskogo str. 17, Vladivostok, 690041, Russia.
  • 7 Far Eastern Branch, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Russian Academy of Science, 159, Pr. 100 let Vladivostoku, Vladivostok, 690022, Russia. daminin@piboc.dvo.ru.
  • 8 Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Sanmin District, Kaohsiung City, 80708, Taiwan. daminin@piboc.dvo.ru.
  • 9 Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan. ymwang@nycu.edu.tw.
  • 10 Center for Intelligent Drug Systems and Smart Bio-devices (IDS²B), National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan. ymwang@nycu.edu.tw.
  • # Contributed equally.
PMID: 38001420 DOI: 10.1186/s12935-023-03141-z
Abstract

Background: Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors.

Methods: To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A2-2 (CA2-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage. The polarization of CA2-2-pretreated macrophages was analyzed by flow cytometry and confocal imaging. The anti-cancer activity of CA2-2 macrophages was evaluated against 4T1 breast Cancer cells and EAC cells in vitro and syngeneic mouse model in vivo.

Results: Incubation of murine macrophages with CA2-2 led to polarization into the M1 phenotype, and the CA2-2-pretreated macrophages could selectively target and kill various types of Cancer in vitro. Notably, loading near-infrared (NIR) fluorochrome-labeled nanoparticles, MnMEIO-mPEG-CyTE777, into macrophages substantiated that M1 macrophages can target and penetrate tumor tissues in vivo efficiently.

Conclusion: In this study, CA2-2-polarized M1 macrophages significantly attenuated tumor growth and prolonged mice survival in the syngeneic mouse models. Therefore, ex vivo CA2-2 activation of mouse macrophages can serve as a useful model for subsequent antitumor cellular immunotherapy developments.

Keywords

Anticancer; Cucumarioside A2-2; Holothurian triterpene glycoside; Immunotherapy; M1 macrophage.

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