BioCentury
ARTICLE | Preclinical News

UW team builds protein that avoids IL-2 toxicities, forms Neoleukin to develop

January 11, 2019 12:44 AM UTC

University of Washington researchers published a Nature paper Wednesday detailing the construction of a synthetic protein that selectively binds to IL-2 to avoid toxicities that have previously overshadowed interest in the receptor as a therapeutic target. Several of the study authors have formed Neoleukin Therapeutics Inc. (Seattle, Wash.) to develop the synthetic protein, dubbed NEO-201.

Because the IL-2 receptor has two variants expressed on different cell types, targeting the receptor can lead to severe toxicities, including life-threatening pulmonary edema, hypotension and capillary leak syndrome. Binding to the intermediate-affinity form -- comprising CD122 and CD132 -- found on CD8+ T cells and NK cells stimulates proliferation and activation of the tumor-killing cells. But IL-2 preferentially binds high-affinity receptors, which include CD25, on Tregs, inducing proliferation of the immunosuppressive cells and potentially counteracting the effects of the cytotoxic T and NK cells (see "Clever Pegylation Pay Off")...