90 : High efficiency targeting of interferon ¦Á activity

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• 作者：Genevi¨¨ve Garcin ; Franciane Paul ; Markus Staufenbiel ; Yann Bordat ; Jos¨¦ Van der Heyden ; Stephan Wilmes ; Guillaume Cartron ; Florence Apparailly ; Stefaan De Koker ; Jacob Piehler ; Jan Tavernier ; Gilles Uz¨¦
• 刊名：Cytokine
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：63
• 期：3
• 页码：264
• 全文大小：40 K

文摘

Systemic toxicity currently prevents full clinical application of type I interferons (IFNs) for the treatment of cancers and viral infections. Although the use of IFNs fused to antibodies resulted in a 10-fold increased activity towards targeted cells, off-target side effects experienced by the patients are expected to remain a major obstacle. We present a novel strategy to engineer IFN¦Á with high in vitro and in vivo activity towards cells expressing a specific surface marker while having an up to 1000-fold reduced activity towards non-relevant cells. The concept lies in the use of immunocytokines based on IFN mutants with strongly reduced binding affinity for the IFN receptor. Such a targeted IFN recovers almost maximally its antiviral activity uniquely on the targeted cells and acts to selected cell populations in mice with targeting efficiencies up to 3 orders of magnitude. This novel concept holds promise to revitalize the clinical potential of IFN¦Á and other cytokines.