title: Surrogate target cells expressing surface anti-idiotype antibody for the clinical evaluation of an internalizing CD22-specific antibody.
abstract: SM03, a chimeric antibody that targets the B-cell restricted antigen CD22, is currently being clinically evaluated for the treatment of lymphomas and other autoimmune diseases in China. SM03 binding to surface CD22 leads to rapid internalization, making the development of an appropriate cell-based bioassay for monitoring changes in SM03 bioactivities during production, purification, storage, and clinical trials difficult. We report herein the development of an anti-idiotype antibody against SM03. Apart from its being used as a surrogate antigen for monitoring SM03 binding affinities, the anti-idiotype antibody was engineered to express as fusion proteins on cell surfaces in a non-internalizing manner, and the engineered cells were used as novel "surrogate target cells" for SM03. SM03-induced complement-mediated cytotoxicity (CMC) against these "surrogate target cells" proved to be an effective bioassay for monitoring changes in Fc functions, including those resulting from minor structural modifications borne within the Fc-appended carbohydrates. The approach can be generally applied for antibodies that target rapidly internalizing or non-surface bound antigens. The combined use of the anti-idiotype antibody and the surrogate target cells could help evaluate clinical parameters associated with safety and efficacies, and possibly the mechanisms of action of SM03.
authors.affiliation: a Institute of Biomedical Sciences ; Fudan University ; Shanghai , China.
authors.forename: Shui-On
authors.initials: SO
authors.lastname: Leung
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.forename: Guang Yu
authors.initials: GY
authors.lastname: Wang
authors.forename: Benny Ka-Wa
authors.initials: BK
authors.lastname: Cheung
authors.forename: Kwan-Yeung
authors.initials: KY
authors.lastname: Lee
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Wing-Tai
authors.initials: WT
authors.lastname: Cheung
authors.forename: Jun Zhi
authors.initials: JZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry* / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000737:chemistry* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000276:immunology; D001681:Biological Assay; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000276:immunology; D008297:Male; D051379:Mice; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry* / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C497867:CD22 protein, human; D007141:Immunoglobulin Fc Fragments; D051918:Sialic Acid Binding Ig-like Lectin 2
keywords: ADCC, antibody dependent cell cytotoxicity; CD22; CMC, complement mediated cytotoxicity; HACA, human anti-chimeric antibody; MOA, mechanism of action; NHL, non-Hodgkins lymphoma; PBMC, peripheral blood mononuclear cell; PK, pharmacokinetic; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; anti-idiotype; bioassay; internalizing; mAb, monoclonal antibody; surrogate target cells