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Human Serum Albumin‐Based Drug‐Free Macromolecular Therapeutics: Apoptosis Induction by Coiled‐Coil‐Mediated Cross‐Linking of CD20 Antigens on Lymphoma B Cell Surface
Author(s) -
Zhang Libin,
Fang Yixin,
Li Lian,
Yang Jiyuan,
Radford D. Christopher,
Kopeček Jindřich
Publication year - 2018
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201800224
Subject(s) - raji cell , chemistry , cd20 , microbiology and biotechnology , colocalization , apoptosis , antigen , cell , biochemistry , biology , immunology
A therapeutic platform—drug‐free macromolecular therapeutics (DFMT)—that induces apoptosis in B cells by cross‐linking of CD20 receptors, without the need for low molecular weight cytotoxic drug, is developed. In this report, a DFMT system is synthesized and evaluated based on human serum albumin (HSA) and two complementary coiled‐coil forming peptides, CCE and CCK. Fab′ fragment of anti‐CD20 monoclonal antibody rituximab is attached to CCE (Fab′‐CCE); multiple grafts of CCK are conjugated to HSA (HSA‐(CCK) 7 ). The colocalization of both nanoconjugates at the surface of non‐Hodgkin’s lymphoma (NHL) Raji cells is demonstrated by confocal fluorescence microscopy. The colocalization leads to coiled‐coil formation, CD20 cross‐linking, and apoptosis induction. The apoptotic levels are evaluated by Annexin V, Caspase 3, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Selective surface binding of DFMT to CD20+ cells is validated in experiments on a coculture of CD20+ (Raji) and CD20‐(DG‐75) cells. It is found that DFMT can trigger calcium influx only in Raji cells, but not in DG‐75 cells. A highly specific treatment for NHL and other B cell malignancies with considerable translational potential is presented by HSA‐based DFMT system.