Year: 2026
Type: preprint
Abstract: Dendritic cells (DCs) are central orchestrators of anti-tumor immunity, yet their therapeutic utility has been limited by dysfunction and insufficient activation within solid tumors. Here, we report chimeric antigen receptor-engineered DCs (CAR-DCs) that potently prime T cells and reprogram the tumor microenvironment. We identify the intracellular domains of CLEC9A or DEC205 as essential for functional CAR-DC activity, enabling enhanced antigen uptake, cross-presentation, and robust cytokine production that drive strong T cell expansion and effector differentiation. Mechanistically, CARs incorporating CLEC9A or DEC205 intracellular domains triggered SYK phosphorylation and downstream signaling pathways. In both murine and humanized models, CAR-DC therapy suppressed tumor growth and promoted expansion of tumor-reactive T cells. These findings establish CAR-DCs as a scalable and clinically translatable platform for next-generation solid tumor immunotherapy.
Source: Research Square
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Ludwig Institute for Cancer Research, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Natural Science Foundation of China, Government of Jiangsu Province, Natural Science Foundation of Jiangsu Province, Hyderabad Eye Research Foundation, Hôpitaux Universitaires de Genève, Fondation ISREC, National Key Research and Development Program of China
OpenAlex ID: W7130381110