한빛사논문
- 조회750
Jaehyun Kim1, Minjeong Kim1, Seok-Beom Yong2, Heesoo Han1, Seyoung Kang1, Shayan Fakhraei Lahiji1,4, Sangjin Kim1, Juhyeong Hong1, Yuha Seo1 and Yong-Hee Kim1,3,4*
1Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 04763, Republic of Korea
2Nucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungcheongbuk-do 28116, Republic of Korea
3Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul 04763, Republic of Korea
4Cursus Bio Inc. Icure Tower, Gangnam-gu, Seoul 06170, Republic of Korea
*Correspondence: Yong-Hee Kim
Abstract
Background: The emergence of cancer immunotherapies, notably immune checkpoint inhibitors, has revolutionized anti-cancer treatments. These treatments, however, have been reported to be effective in a limited range of cancers and cause immune-related adverse effects. Thus, for a broader applicability and enhanced responsiveness to solid tumor immunotherapy, immunomodulation of the tumor microenvironment is crucial. Transforming growth factor-β (TGF-β) has been implicated in reducing immunotherapy responsiveness by promoting M2-type differentiation of macrophages and facilitating cancer cell metastasis.
Methods: In this study, we developed macrophage membrane-coated nanoparticles loaded with a TGF-βR1 kinase inhibitor, SD-208 (M[Formula: see text]-SDNP). Inhibitions of M2 macrophage polarization and epithelial-to-mesenchymal transition (EMT) of cancer cells were comprehensively evaluated through in vitro and in vivo experiments. Bio-distribution study and in vivo therapeutic effects of M[Formula: see text]-SDNP were investigated in orthotopic breast cancer model and intraveneously injected metastasis model.
Results: M[Formula: see text]-SDNPs effectively inhibited cancer metastasis and converted the immunosuppressive tumor microenvironment (cold tumor) into an immunostimulatory tumor microenvironment (hot tumor), through specific tumor targeting and blockade of M2-type macrophage differentiation. Administration of M[Formula: see text]-SDNPs considerably augmented the population of cytotoxic T lymphocytes (CTLs) in the tumor tissue, thereby significantly enhancing responsiveness to immune checkpoint inhibitors, which demonstrates a robust anti-cancer effect in conjunction with anti-PD-1 antibodies.
Conclusion: Collectively, responsiveness to immune checkpoint inhibitors was considerably enhanced and a robust anti-cancer effect was demonstrated with the combination treatment of M[Formula: see text]-SDNPs and anti-PD-1 antibody. This suggests a promising direction for future therapeutic strategies, utilizing bio-inspired nanotechnology to improve the efficacy of cancer immunotherapy.
논문정보
- Research article
- 2023년 12월 (BRIC 등록일 2023-12-20)
- 국내 연구진
- 생명과학 > 생물공학
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