Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy.
Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy.
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DOI：
10.1038/ncomms12878
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发表时间：
2016-09-21
影响因子：
16.6
通讯作者：
Krupnick, Alexander Sasha
中科院分区：
文献类型：
--
作者：
Ghasemi, Reza;Lazear, Eric;Wang, Xiaoli;Arefanian, Saeed;Zheleznyak, Alexander;Carreno, Beatriz M.;Higashikubo, Ryuji;Gelman, Andrew E.;Kreisel, Daniel;Fremont, Daved H.;Krupnick, Alexander Sasha
Despite over 20 years of clinical use, IL-2 has not fulfilled expectations as a safe and effective form of tumour immunotherapy. Expression of the high affinity IL-2Rα 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-2Rα. 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-2Rα-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. High-affinity IL-2Rα expressed by Tregs mitigates the potential of IL-2 use in cancer therapy. Here, the authors fuse IL-2 with an NKDG2 binding domain, and show that it induces IL-2 signalling selectively in NKG2D+ cells, delaying tumour growth in mice without the side effects of conventional IL-2 therapy.
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影响因子：
--
作者：
Haan, Claude;Rolvering, Catherine;Zerwes, Hans-Guenter
通讯作者：
Zerwes, Hans-Guenter
DOI：
10.1073/pnas.0909384107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Letourneau, Sven;van Leeuwen, Ester M. M.;Boyman, Onur
通讯作者：
Boyman, Onur
影响因子：
5.8
作者：
Frese-Schaper, Manuela;Keil, Andreas;Frese, Steffen
通讯作者：
Frese, Steffen
影响因子：
11.2
作者：
Kreisel D;Gelman AE;Higashikubo R;Lin X;Vikis HG;White JM;Toth KA;Deshpande C;Carreno BM;You M;Taffner SM;Yokoyama WM;Bui JD;Schreiber RD;Krupnick AS
通讯作者：
Krupnick AS
影响因子：
7.8
作者：
HEMAR, A;SUBTIL, A;LIEB, M;MORELON, E;HELLIO, R;DAUTRYVARSAT, A
通讯作者：
DAUTRYVARSAT, A