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2. 发明申请

WO2012044999A2 REVERSIBLE PROTEIN MULTIMERS, METHODS FOR THEIR PRODUCTION AND USE 审中-公开
标题翻译：可逆蛋白多体，其生产和使用方法
公开(公告)号：WO2012044999A2
公开(公告)日：2012-04-05
申请号：PCT/US2011/054335
申请日：2011-09-30
申请人： LUDWIG INSTITUTE FOR CANCER RESEARCH LTD. , LUESCHER, Immanuel, F. , SCHMIDT, Julien , GUILLAUME, Philippe , DOJCINOVIC, Danijel
发明人： LUESCHER, Immanuel, F. , SCHMIDT, Julien , GUILLAUME, Philippe , DOJCINOVIC, Danijel
IPC分类号： A61K39/385
CPC分类号： C07K17/00 , A61K39/00 , A61K39/385 , A61K2039/605 , A61K2039/627 , A61K2039/64 , C07K14/70539
摘要： Some aspects of this invention are based on the recognition that reversible protein multimers in which monomeric proteins are conjugated to a carrier molecule via chelation complex bonds are stable under physiological conditions and can be dissociated in a controlled manner under physiological, nontoxic conditions. Accordingly, such protein multimers are useful for a variety of in vitro, ex vivo, and in vivo application for research, diagnostics, and therapy. Some aspect of this invention provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor- mediated T-cell activation can be minimized. The use of reversible MHC multimers as provided herein, accordingly, allows for the detection and isolation of bona fide antigen- specific CD8+ T cells without inducing activation dependent cell death, including rare, therapeutically valuable T- cells expressing T-cell receptors binding tumor antigens with high affinity. Methods for the production and use of reversible multimers are also provided.
摘要翻译：本发明的一些方面基于以下认识：其中单体蛋白经由螯合络合物键与载体分子缀合的可逆蛋白多聚体在生理条件下是稳定的，并且可以以受控方式解离生理的，无毒的条件。因此，这样的蛋白质多聚体可用于各种体外，离体和体内应用于研究，诊断和治疗。本发明的一些方面提供了可逆的MHC蛋白质多聚体，以及在检测和/或分离特定的T细胞或T细胞群中使用此类多聚体的方法。因为可逆的MHC多聚体可以有效地解离，所以MHC与T细胞受体结合的时间以及因此T细胞受体介导的T细胞活化的时间可以最小化。因此，本文提供的可逆MHC多聚体的使用允许检测和分离真正的抗原特异性CD8 + T细胞而不诱导活化依赖性细胞死亡，包括表达罕见的治疗上有价值的T细胞表达 T细胞受体以高亲和力结合肿瘤抗原。还提供了生产和使用可逆多聚体的方法。

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