Surrogate target cells expressing surface anti-idiotype antibody for the clinical evaluation of an internalizing CD22-specific antibody
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AbstractSM03, 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.
All Author(s) ListLeung SO, Gao K, Wang GY, Cheung BKW, Lee KY, Zhao Q, Cheung WT, Wang JZ
Journal namemAbs
Detailed descriptionTo ORKTS: Mr. Kwan-yeung Lee was a undergraduate student of the Biotech programme who worked on the project in Prof. W.T. Cheung's lab as a summer stu
Year2015
Month1
Day1
Volume Number7
Issue Number1
PublisherTaylor & Francis: STM, Behavioural Science and Public Health Titles
Pages66 - 76
ISSN1942-0862
eISSN1942-0870
LanguagesEnglish-United Kingdom
KeywordsADCC; anti-idiotype; antibody dependent cell cytotoxicity; bioassay; CD22; CMC; complement mediated cytotoxicity; HACA; human anti-chimeric antibody; internalizing; mAb; mechanism of action; MOA; monoclonal antibody; NHL; non-Hodgkins lymphoma; PBMC; peripheral blood mononuclear cell; pharmacokinetic; PK; RA; rheumatoid arthritis; SLE; surrogate target cells; systemic lupus erythematosus
Web of Science Subject CategoriesMedicine, Research & Experimental; Research & Experimental Medicine

Last updated on 2020-21-09 at 00:50