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Expression of the high affinity IL-2R\u03b1 chain on regulatory T cells mitigates the anti-tumour immune response and its expression on vascular endothelium is responsible for life threatening complications such as diffuse capillary leak and pulmonary oedema. Here we describe the development of a recombinant fusion protein comprised of a cowpox virus encoded NKG2D binding protein (OMCP) and a mutated form of IL-2 with poor affinity for IL-2R\u03b1. This fusion protein (OMCP-mutIL-2) potently and selectively activates IL-2 signalling only on NKG2D-bearing cells, such as natural killer (NK) cells, without broadly activating IL-2R\u03b1-bearing cells. OMCP-mutIL-2 provides superior tumour control in several mouse models of malignancy and is not limited by mouse strain-specific variability of NK function. In addition, OMCP-mutIL-2 lacks the toxicity and vascular complications associated with parental wild-type IL-2.<\/jats:p>","DOI":"10.1038\/ncomms12878","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T06:28:15Z","timestamp":1474439295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy"],"prefix":"10.1038","volume":"7","author":[{"given":"Reza","family":"Ghasemi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lazear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Arefanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Zheleznyak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz M.","family":"Carreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Higashikubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E.","family":"Gelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kreisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daved H.","family":"Fremont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Sasha","family":"Krupnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,21]]},"reference":[{"key":"BFncomms12878_CR1","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.immuni.2015.04.015","volume":"42","author":"JB Spangler","year":"2015","unstructured":"Spangler, J. 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D.H.F. and A.S.K. have filed a patent on data described in this manuscript with technology licensed to Courier Therapeutics (http:\/\/www.couriertherapeutics.com). Targeted Cytokine Delivery to Cytotoxic Lymphocytes-Inventors: Alexander S. Krupnick, Daved H. Fremont, Eric Lazear, U.S. Provisional Application number 62\/091,898, filed December 15, 2014.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12878"}}