Abstract
<div>Abstract<p>Recruitment of immune cells to tumor cells targeted by a therapeutic antibody can heighten the antitumor efficacy of the antibody. For example, p185<i><sup>her2/neu</sup></i>-targeting antibodies not only downregulate the p185<i><sup>her2/neu</sup></i> kinase (ERBB2) but also trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) through the antibody Fc region. Here, we describe a generalized strategy to improve immune cell recruitment to targeted cancer cells, using a modified scFv antibody we call a “Grababody” that binds the target protein and endogenous immunoglobulins. The model system we used to illustrate the use of this platform recognizes p185<i><sup>her2/neu</sup></i> and includes an IgG binding domain. The recombinant scFv Grababody that was created recruited circulating human IgGs and attracted immune cells carrying Fc receptors to tumor cells that expressed p185<i><sup>her2/neu</sup></i>. The presence of the IgG binding domain significantly enhanced CDC and ADCC activity and improved antitumor activity <i>in vivo</i>. Our results illustrate a novel general approach to improve antibody-like proteins for therapeutic applications. <i>Cancer Res; 73(8); 2619–27. ©2013 AACR</i>.</p></div>
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