한빛사논문
- 조회1,344
Mikyung Kang1, Seong Ho Lee2, Miji Kwon2, Junho Byun3, Dongyoon Kim3, Cheesue Kim4, Sagang Koo5,6, Sung Pil Kwon4, Sangjun Moon4, Mungyo Jung4, Jihye Hong1, Seokhyeong Go1, Seuk Young Song4, Jae Hyun Choi3, Taeghwan Hyeon5,6, Yu-Kyoung Oh3, Hee Ho Park7,8,* Byung-Soo Kim1,4,9,*
1Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.
2Department of Smart Health Science and Technology, Kangwon National University, Chuncheon, 24341, Republic of Korea.
3College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
4School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
5Center for Nanoparticle Research, Institute of Basic Science (IBS), Seoul, 08826, Republic of Korea.
6School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea.
7Department of Bioengineering, Hanyang University, Seoul, 04763, Republic of Korea.
8Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea.
9Institute of Chemical Processes, Institute of Engineering Research, BioMAX, Seoul National University, Seoul, 08826, Republic of Korea.
M.K. and S.H.L. contributed equally to this work.
*To whom correspondence should be addressed.
Abstract
Chimeric antigen receptor-T (CAR-T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to its complex ex vivo cell-manufacturing procedures and low therapeutic efficacy against solid tumors. The limited therapeutic effects are partially due to limited CAR-T cell infiltration to solid tumors and inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented to in vivo program macrophages, which can intrinsically penetrate solid tumors, into CAR-M1 macrophages displaying enhanced cancer-directed phagocytosis and anti-tumor activity. In vivo injected nanocomplexes of macrophage-targeting nanocarriers and CAR-interferon-γ-encoding plasmid DNA induce CAR-M1 macrophages that are capable of CAR-mediated cancer phagocytosis, anti-tumor immunomodulation, and inhibition of solid tumor growth. Together, this study describes an off-the-shelf CAR-macrophage therapy that is effective for solid tumors and avoids the complex and costly processes of ex vivo CAR-cell manufacturing.
논문정보
- Research article
- 2021년 09월 (BRIC 등록일 2021-09-16)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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