Rewiring dendritic cell function with CLEC9A and DEC205 CARs.

CAR-engineered dendritic cells using CLEC9A or DEC205 intracellular domains enhance antigen uptake and cross-presentation, linked to SYK phosphorylation and stronger antitumor T-cell responses in mouse models.

• Why it matters: Solid tumors often impair dendritic cell function and activation, limiting antitumor immunity; this work targets that dysfunction with a programmable DC platform.
• What they did: The study built CAR-DCs using intracellular domains from CLEC9A or LY75 (DEC205), then tested whether these domains support SYK phosphorylation, antigen uptake, cross-presentation, and T-cell expansion in conventional and humanized mice.
• The result: In both conventional and humanized mouse models, CAR-DC therapy suppressed tumor growth and promoted expansion of tumor-reactive T cells, supporting clinical translation for solid tumors.

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