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Engineering macrophage-targeted trispecific immune cell engagers for tumor immunotherapy

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Nature Biotechnology, Published online: 30 March 2026; doi:10.1038/s41587-026-03104-5

Immune cell engagers (ICEs) have emerged as a promising strategy for cancer immunotherapy, but their efficacy in solid tumors remains limited, partly as a result of the difficulty of coordinating activating and inhibitory signals within the same immune cell. Here, we report a logic-gated cis-targeting strategy that enables ICEs to coordinate activating and inhibitory signals within macrophages, thereby enhancing tumor clearance in mouse models of solid cancers.

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