title: scFv-based "Grababody" as a general strategy to improve recruitment of immune effector cells to antibody-targeted tumors.
abstract: Recruitment of immune cells to tumor cells targeted by a therapeutic antibody can heighten the antitumor efficacy of the antibody. For example, p185(her2/neu)-targeting antibodies not only downregulate the p185(her2/neu) 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(her2/neu) 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(her2/neu). The presence of the IgG binding domain significantly enhanced CDC and ADCC activity and improved antitumor activity in vivo. Our results illustrate a novel general approach to improve antibody-like proteins for therapeutic applications.
authors: Department of Pathology and Lab Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: Zheng
authors: Z
authors: Cai
authors: Ting
authors: T
authors: Fu
authors: Yasuhiro
authors: Y
authors: Nagai
authors: Lian
authors: L
authors: Lam
authors: Marla
authors: M
authors: Yee
authors: Zhiqiang
authors: Z
authors: Zhu
authors: Hongtao
authors: H
authors: Zhang
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003167:Complement Activation; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D057127:Single-Chain Antibodies
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