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- W2912251014 abstract "Receptors that help immune cells recognize ‘self’ cells can be functionally blocked with antibodies, and a fraction of cancer patients show durable cures through blockade of such T-cell checkpoints. Macrophages possess a similar checkpoint that we block in combination with tumor opsonization in order to target injected macrophages for phagocytosis of cancer cells. The approaches require immune cell infiltration, which motivates study of the physical properties of tumors. We are specifically blocking signal regulatory protein alpha (SIRPα) on macrophages, which binds the ubiquitous ‘self’-marker CD47, and we inject these cells together with a pro-phagocytic antibody against tyrosinase-related protein 1 (Tyrp1) on syngeneic B16 melanoma in an immunocompetent mouse. This widely used preclinical murine model for evaluating immunotherapies is sometimes described as a ‘solid’ tumor, but macropipette aspiration of fresh tumors reveals high compliance and largely irreversible deformation. Such properties will generally modulate macrophage infiltration, interactions, and phenotype. As we continue to study such effects, we already find that systematic injection of engineered macrophages into mice with subcutaneous B16 tumors results in delayed tumor growth and even some durable cures." @default.
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- W2912251014 date "2019-02-01" @default.
- W2912251014 modified "2023-09-26" @default.
- W2912251014 title "Macrophage Checkpoint Blockade and Tumor Mechanics in a Cell-Based Immunotherapy" @default.
- W2912251014 doi "https://doi.org/10.1016/j.bpj.2018.11.3108" @default.
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