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
Rok vydání: 2021
Předmět:
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