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. 2021 Oct;33(43):e2103258.
doi: 10.1002/adma.202103258. Epub 2021 Sep 12.

Nanocomplex-Mediated In Vivo Programming to Chimeric Antigen Receptor-M1 Macrophages for Cancer Therapy

Mikyung Kang  1 , Seong Ho Lee  2 , Miji Kwon  2 , Junho Byun  3 , Dongyoon Kim  3 , Cheesue Kim  4 , Sagang Koo  5   6 , Sung Pil Kwon  4 , Sangjun Moon  4 , Mungyo Jung  4 , Jihye Hong  1 , Seokhyeong Go  1 , Seuk Young Song  4 , Jae Hyun Choi  3 , Taeghwan Hyeon  5   6 , Yu-Kyoung Oh  3 , Hee Ho Park  7   8 , Byung-Soo Kim  1   4   9
Affiliations

Nanocomplex-Mediated In Vivo Programming to Chimeric Antigen Receptor-M1 Macrophages for Cancer Therapy

Mikyung Kang et al. Adv Mater. 2021 Oct.

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.

Keywords: CAR-macrophage; DNA/polymer nanocomplex; cancer therapy; cytotoxic T lymphocyte; in situ transfection.

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