POSTER SESSION: New Therapies in Immuno-Oncology| Volume 138, SUPPLEMENT 2, S57, October 2020

Emergence of novel long-acting mono- and bi-specific IL-2/IL-13 superkines as potent immune modulators

      Background: Use of IL-2 (Proleukin) remains limited due to a short half-life, toxicity, and preferential activation of Tregs driven by a high affinity for IL2Rα over IL2Rβ. To bypass these limitations, we further engineered MDNA109, an IL-2 superkine, to generate MDNA11 by (1) addition of mutations to abrogate IL2Rα binding and (2) fusion with albumin to extend half-life. We also leveraged the versatility of our superkine platforms to engineer long-acting bispecific constructs to simultaneously activate IL-2 signaling (i.e. pro-inflammatory) and suppress IL-4/IL-13 function (i.e. anti-inflammatory) and/ or enable accumulation in tumors.
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