Sustained Release of IL-2 Using an Injectable Hydrogel Prevents Autoimmune Diabetes

Nagy, N.; Kaber, G.; Kratochvil, M.; Kuipers, H.; Ruppert, S.; Yadava, K.; Yang, J.; Heilshorn, S.; Long, A.; Pugliese, A.; Bollyky, P.

doi:10.1101/2020.03.15.993063

bioRxiv · 10.1101/2020.03.15.993063

Sustained Release of IL-2 Using an Injectable Hydrogel Prevents Autoimmune Diabetes

Nagy, N.·Kaber, G.·Kratochvil, M.·Kuipers, H.·Ruppert, S.·Yadava, K.·Yang, J.·Heilshorn, S.·Long, A.·Pugliese, A.·Bollyky, P.

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Abstract

Interleukin 2 (IL-2) is a promising therapy for autoimmune type 1 diabetes (T1D), but the short half-life in vivo (less than 6 minutes) limits effective tissue exposure to IL-2. Tissue exposure is required for the tolerogenic effects of IL-2. We have developed an injectable hydrogel that incorporates heparin polymers to enable the sustained release of IL-2. This platform uses clinical grade and commercially available materials, including collagen, hyaluronan, and heparin, to deliver IL-2 by slowly degrading and releasing IL-2 over a two-week period in vivo. We find that heparin potentiates the activity of IL-2 and IL-2-mediated expansion of Foxp3+ regulatory T cell (Treg). Hydrogel-mediated IL-2 release showed a reduction of CD4+ and CD8+ T cells and an increase of FoxP3+ Treg in the lymph nodes of injected mice. Moreover, in the Non-Obese Diabetic (NOD) mouse model of T1D once-weekly administration of IL-2 hydrogels prevented diabetes onset as efficiently as 3x weekly repeated injections of soluble IL-2. Together these data suggest that heparin-containing hydrogels may have benefit in delivering low-dose IL-2 and promoting immune tolerance in autoimmune diabetes.

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Nagy, N., Kaber, G., Kratochvil, M., Kuipers, H., Ruppert, S., Yadava, K., Yang, J., Heilshorn, S., Long, A., Pugliese, A., Bollyky, P.. 2020-03-18. Sustained Release of IL-2 Using an Injectable Hydrogel Prevents Autoimmune Diabetes. https://doi.org/10.1101/2020.03.15.993063

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