Engineered Macrophage via Click Chemistry Enhances Tumor Targeting and Remodels Immunosuprressive Tumor Microenvironment
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초록
내용
A cell-based drug delivery system has been developed as an alternative drug carriers using immune cells, such as dendritic cells (DCs), macrophages, and T cells. Cell therapy is more specific and lower side effects than small-molecule based drugs because of the sensitive and specific characteristics of cells. In this study, we developed a novel engineered macrophage which specifically bind to DBCO-labelled liposome(3M-052) by click chemistry. Azido-labelled M1 macrophages which migrate to the tumor tissues were obtained from BMDM treated with tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) and lipopolysaccharide (LPS). Intravenous injection of liposome(3M-052) anchored macrophage increased tumor accumulation and reshaped immunosuppressive tumor microenvironment (TME). M1 macrophage used as “transporting cells” also promotes repolarization of M2 to M1 macrophages and 3M-052, the multifaceted immunomodulator TLR7/8a, re-educates immune suppressive cells in TME.