Combination strategies to enhance antitumor ADCC.
Combination strategies to enhance antitumor ADCC.
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DOI：
10.2217/imt.12.38
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发表时间：
2012-05
期刊：
影响因子：
2.8
通讯作者：
Brody J
中科院分区：
文献类型：
--
作者：
Kohrt HE;Houot R;Marabelle A;Cho HJ;Osman K;Goldstein M;Levy R;Brody J
单克隆抗体作为癌症治疗剂的临床功效在很大程度上取决于它们靶向肿瘤并诱导功能性抗肿瘤免疫应答的能力。ADCC的这两步过程利用先天免疫细胞的应答来提供由抗体的Fc部分与免疫细胞上的Fc受体的相互作用触发的抗肿瘤细胞毒性。靶向NK细胞、γδ T细胞、巨噬细胞和树突细胞的免疫治疗剂可以通过增强免疫应答的功能来增强抗体的抗肿瘤活性。这种组合策略的优势包括：应用于多种现有抗体（甚至跨越多种疾病），与先前批准的药物组合的可行性（从监管角度来看）以及保证（医生和试验参与者）其中一种成分-抗肿瘤抗体-已证明其自身有效。在这里，我们讨论了目前的策略，包括生物学原理和临床结果，增强ADCC在以下方面：策略，增加总的目标单克隆抗体效应器结合，策略，触发效应细胞的“激活”信号和策略，阻断效应细胞的“抑制”信号。
The clinical efficacy of monoclonal antibodies as cancer therapeutics is largely dependent upon their ability to target the tumor and induce a functional antitumor immune response. This two-step process of ADCC utilizes the response of innate immune cells to provide antitumor cytotoxicity triggered by the interaction of the Fc portion of the antibody with the Fc receptor on the immune cell. Immunotherapeutics that target NK cells, γδ T cells, macrophages and dendritic cells can, by augmenting the function of the immune response, enhance the antitumor activity of the antibodies. Advantages of such combination strategies include: the application to multiple existing antibodies (even across multiple diseases), the feasibility (from a regulatory perspective) of combining with previously approved agents and the assurance (to physicians and trial participants) that one of the ingredients – the antitumor antibody – has proven efficacy on its own. Here we discuss current strategies, including biologic rationale and clinical results, which enhance ADCC in the following ways: strategies that increase total target–monoclonal antibody–effector binding, strategies that trigger effector cell ‘activating’ signals and strategies that block effector cell ‘inhibitory’ signals.
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影响因子：
20.3
作者：
Angelini, DF;Borsellino, G;Battistini, L
通讯作者：
Battistini, L
DOI：
10.3324/haematol.2010.029520
发表时间：
2011-03-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Braza, Mounia Sabrina;Klein, Bernard;Rossi, Jean-Francois
通讯作者：
Rossi, Jean-Francois
影响因子：
11.5
作者：
Ansell, Stephen M.;Geyer, Susan M.;Witzig, Thomas E.
通讯作者：
Witzig, Thomas E.
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.4
作者：
Buechele, C.;Baessler, T.;Salih, H. R.
通讯作者：
Salih, H. R.