Nanocomplex‐Mediated In Vivo Programming to Chimeric Antigen Receptor‐M1 Macrophages for Cancer Therapy
| Autor: | Yu-Kyoung Oh, Dongyoon Kim, Sagang Koo, Mikyung Kang, Mungyo Jung, Junho Byun, Hee Ho Park, Sung Pil Kwon, Jihye Hong, Seuk Young Song, Seokhyeong Go, Cheesue Kim, Miji Kwon, Byung-Soo Kim, Jae Hyun Choi, Sangjun Moon, Taeghwan Hyeon, Seong Ho Lee |
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| Rok vydání: | 2021 |
| Předmět: |
Tumor microenvironment
Receptors Chimeric Antigen Materials science Mechanical Engineering medicine.medical_treatment Immunotherapy Chimeric antigen receptor Antigen Mechanics of Materials In vivo medicine Cancer research Cytotoxic T cell General Materials Science Nanocarriers human activities Ex vivo |
| Zdroj: | Advanced Materials. 33:2103258 |
| ISSN: | 1521-4095 0935-9648 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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