Tumor immune cell targeting chimeras reprogram tumor-associated macrophages.

Tumor immune cell targeting chimeras (TICTACs) selectively deplete immune checkpoint receptors from tumor-associated macrophages, driving robust checkpoint degradation in CD206 high cells (up to 50% of solid tumor mass).

• Why it matters: Systemic immune checkpoint blockade can cause immune-related adverse events, and TAMs are a dominant tumor microenvironment population linked to immunosuppression and tumorigenesis.
• What they did: TICTACs use a synthetic ligand targeting CD206 conjugated to a nonblocking antibody that binds checkpoint receptors like SIRPα, aiming to degrade receptors via CD206 recycling.
• The result: Engaging CD206 drives robust checkpoint degradation in CD206 high macrophages with no effect on CD206 low cells, enabling tumor-specific immunotherapy without blocking function.

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