title: Nonfucosylated anti-CD20 antibody potentially induces apoptosis in lymphoma cells through enhanced interaction with FcgammaRIIIb on neutrophils.
abstract: We demonstrate herein the augmentation of rituximab-mediated apoptosis in lymphoma cell lines by cross-linking with recombinant FcgammaRs, which is further enhanced by using a nonfucosylated variant of rituximab having strong FcgammaRIII-binding capacity. Furthermore, we show that neutrophils can serve as physiological cross-linkers that augment anti-CD20-mediated apoptosis, as evidenced by (i) the neutrophil-augmented apoptosis was more profound for the nonfucosylated variant of rituximab and (ii) the mechanism depended on FcgammaRIIIb but not on FcgammaRIIa. Taken together, we suggest a potential anti-tumour mechanism of nonfucosylated anti-CD20 antibody by which antibody molecules are cross-linked through enhanced interaction with FcgammaRIIIb in neutrophils.
authors.affiliation: Antibody Research Laboratories, Research Division, Kyowa Hakko Kirin Co, Ltd, 3-6-6, Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Akito
authors.initials: A
authors.lastname: Natsume
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Satoh
authors.forename: Rinpei
authors.initials: R
authors.lastname: Niwa
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents; D006801:Humans; D008223:Lymphoma / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; C499173:FCGR2B protein, human; D017452:Receptors, IgG; D000069283:Rituximab