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Engineered Tolerogenic Artificial Antigen-presenting Cells for Specific Expansion of Regulatory T Cells
Johns Hopkins University
Cell therapy
Immunology
Hit To Lead or Lead Optimization
• A biodegradable particle comprising a polyester or polyester blend, a first protein that binds to an immune cell, and a second protein that promotes proliferation and / or activation of immune cells, and a third soluble protein or small molecule encapsulated within the particle. The second protein is a fusion protein comprising at least a portion of an antibody and at least a portion of a Cytokine.
• Tolerogenic antigen presenting cells (TolAPCs) consisting of a biodegradable particle surface-conjugated with a combination of IC and autoantigen-loaded MHC tetramers have been developed.
• TolAPCs are synthesized by forming a polymer core and covalently attaching ICs and specific autoantigen complexes to the surface. To evaluate performance, TolAPCs were incubated in-vitro with CD4+ T cells and compared to free IL-2 cytokine and free IC complexes.
• TolAPCs selectively stimulated Treg populations and achieved the same stimulation as free IC and greater stimulation than free IL-2. In an in-vivo mouse model, TolAPCs also increased the ratio of Treg cells compared to a no treatment condition.
• Altogether, the inventors have demonstrated efficacy of TolAPCs as an antigen specific IC based regulatory T cell modulator.
US20220160891A1
Biomimetic tolerogenic artificial antigen presenting cells for regulatory T cell induction. Acta Biomater. (2020)
