Polymer Backpack-Loaded Tissue Infiltrating Monocytes for Treating Cancer.

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Tác giả: Michael Dunne, Alexander P Gottlieb, Jennifer L Guerriero, Neha Kapate, Ninad Kumbhojkar, Samir Mitragotri, Malini Mukherji, Kyung Soo Park, Supriya Prakash, Vineeth Chandran Suja

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Germany : Advanced healthcare materials , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 174292

Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of nonresponders also call for development of antigen-independent therapeutic approaches. Myeloid cells offer such an opportunity, given their large presence in the immunosuppressive tumor microenvironment, such as in triple negative breast cancer. However, their therapeutic utility is hindered by their phenotypic plasticity. Here, the impressive trafficking ability of adoptively transferred monocytes is leveraged into the immunosuppressive 4T1 tumor to develop an antitumor therapy. To control monocyte differentiation in the tumor microenvironment, surface-adherent "backpacks" stably modified with interferon gamma (IFNγ) are developed to stimulate macrophage plasticity into a pro-inflammatory, antitumor phenotype, a strategy as referred to as Ornate Polymer backpacks on Tissue Infiltrating Monocytes (OPTIMs). Treatment with OPTIMs substantially reduces tumor burden in a mouse 4T1 model and significantly increases survival. Cytokine and immune cell profiling reveal that OPTIMs remodeled the tumor microenvironment into a pro-inflammatory state.
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