title: Novel humanized anti-CD20 antibody BM-ca binds to a unique epitope and exerts stronger cellular activity than others.
abstract: Cellular activity of BM-ca, a novel humanized anti-CD20 antibody, was quantitatively compared with that of two other anti-CD20 antibodies used for clinical practice, rituximab and ofatumumab. The results of a complement-dependent cytotoxicity (CDC) assay revealed that the strongest antibody was ofatumumab, followed by BM-ca, with rituximab being the weakest. Ofatumumab and BM-ca were effective not only against rituximab-sensitive SU-DHL-4 cells but also against rituximab-resistant RC-K8 cells. In an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, although the effective concentrations against SU-DHL-4 cells were almost the same among these three antibodies, the maximum cytotoxic level was the highest for BM-ca. In an anti-cell proliferation assay using SU-DHL-4 cells, BM-ca was the most effective and ofatumumab, the weakest. Against RC-K8 cells, only BM-ca was effective. When combined with each of four cancer chemotherapeutics (prednisolone, vincristine, hydroxydaunorubicin, and cisplatin), BM-ca exerted the most effective combinatorial anti-cell proliferation activity. To assess the in vivo effect of BM-ca, we intravenously administered BM-ca into cynomolgus monkeys and found that the peripheral B-cell levels did not decrease in half of the animals. Sequencing of cDNA encoding CD20 of cynomolgus monkeys revealed that the responders and nonresponders had Leu/Pro (hetero) and Leu/Leu (homo) at amino acid (a.a.) position 160, respectively, suggesting that the epitope recognized by BM-ca was around this a.a. By analyzing reactivity to synthetic peptides, the epitope recognized by BM-ca was estimated to be a.a.'s 156-166, not shared with rituximab and ofatumumab. These results suggest BM-ca to be a promising anti-CD20 antibody having superior properties and recognizing a unique epitope.
authors: BioMedics Japan, Inc., 5F, Tokyo-Suisan-Bldg, 4-18, Toyomi-cho, Chuo-ku, Tokyo, 104-0055, Japan.
authors: Hideaki
authors: H
authors: Kobayashi
authors: Yuka
authors: Y
authors: Matsunaga
authors: Yumiko
authors: Y
authors: Uchiyama
authors: Kenji
authors: K
authors: Nagura
authors: Yasuhiko
authors: Y
authors: Komatsu
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003412:Cricetulus; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003630:Daunorubicin / Q000494:pharmacology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008252:Macaca fascicularis; D011239:Prednisolone / Q000494:pharmacology; D000069283:Rituximab; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000939:Epitopes; D000069283:Rituximab; D014750:Vincristine; D011239:Prednisolone; C527517:ofatumumab; D002945:Cisplatin; D003630:Daunorubicin
keywords: Anti-CD20 antibody; cancer chemotherapeutics; epitope; lymphoma; ofatumumab; rituximab
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