title: BM-ca is a newly defined type I/II anti-CD20 monoclonal antibody with unique biological properties.
abstract: Rituximab (chimeric anti-CD20 mAb) is currently used in the treatment of B-NHL and B cell malignancies, alone or in combination with chemotherapy. However, subsets of patients do not initially respond and/or develop resistance to additional treatments. Hence, there is a need to develop more effective anti-CD20 mAbs that may improve clinical response. BM-ca is a novel humanized anti-CD20 mAb that was tested against several B-NHL cell lines and was compared to several anti-CD20 mAbs (Rituximab, ofatumumab, 2H7, B1 and B-Ly1). BM-ca was shown to strongly induce both homotypic cell aggregation and redistribution of CD20 to membrane lipid rafts. BM-ca was also able to induce programmed cell death (apoptosis) without the need for cross-linking and demonstrated potent complement-dependent cytotoxicity (CDC). BM-ca was more cytotoxic than rituximab even in malignant B cells expressing low amounts of membrane CD20. Type I anti-CD20 mAbs typically induce minimal levels of homotypic cell aggregation and apoptosis but strong localization of CD20 to lipid rafts and potent CDC. Type II anti-CD20 mAbs typically exert the reverse activities. Noteworthy, BM-ca exhibits properties that are shared by both type I and type II anti-CD20 mAbs, which may reflect the recognition of a new CD20 epitope and/or exhibit different molecular signaling. Overall, the present data show that BM-ca is a novel anti-CD20 mAb that may be classified as a type I/II. The therapeutics efficacy of BM-ca awaits its use in clinical trials.
authors.affiliation: Late Effects Studies, Radiation Biology Center, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. minishida@aol.com
authors.forename: Michio
authors.initials: M
authors.lastname: Nishida
authors.forename: Norio
authors.initials: N
authors.lastname: Uematsu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Shoko
authors.initials: S
authors.lastname: Ishida
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.forename: Ohtsura
authors.initials: O
authors.lastname: Niwa
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Padlan
authors.forename: Roland
authors.initials: R
authors.lastname: Newman
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015922:Complement C1q / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D021962:Membrane Microdomains / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D015922:Complement C1q