Nanocomplex-Mediated In Vivo Programming to Chimeric Antigen Receptor-M1 Macrophages for Cancer Therapy
- Authors
- Kang, Mikyung; Lee, Seong Ho; Kwon, Miji; Byun, Junho; Kim, Dongyoon; Kim, Cheesue; Koo, Sagang; Kwon, Sung Pil; Moon, Sangjun; Jung, Mungyo; Hong, Jihye; Go, Seokhyeong; Song, Seuk Young; Choi, Jae Hyun; Hyeon, Taeghwan; Oh, Yu-Kyoung; Park, Hee Ho; Kim, Byung-Soo
- Issue Date
- Sep-2021
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- cancer therapy; CAR-macrophage; cytotoxic T lymphocyte; DNA; polymer nanocomplex; in situ transfection
- Citation
- ADVANCED MATERIALS, v.33, no.43, pp.1 - 16
- Indexed
- SCIE
SCOPUS
- Journal Title
- ADVANCED MATERIALS
- Volume
- 33
- Number
- 43
- Start Page
- 1
- End Page
- 16
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/141106
- DOI
- 10.1002/adma.202103258
- ISSN
- 0935-9648
- 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-gamma-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.
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