title: CD48 as a novel molecular target for antibody therapy in multiple myeloma.
abstract: Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34(+)  haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in-house anti-CD48 mAb induced mild antibody-dependent cell-mediated cytotoxicity and marked complement-dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti-CD48 mAb significantly inhibited tumour growth in severe combined immunodeficient mice inoculated subcutaneously with MM cells. Furthermore, anti-CD48 mAb treatment inhibited growth of MM cells transplanted directly into murine bone marrow. Finally and importantly, we demonstrated that the anti-CD48 mAb did not damage normal CD34(+)  haematopoietic stem/progenitor cells. These results suggest that the anti-CD48 mAb has the potential to become an effective therapeutic mAb against MM.
authors.affiliation: Department of Cancer Stem Cell Biology Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan. hnaoki@imed3.med.osaka-u.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ichihara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Mugitani
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishida
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yamagami
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fuji
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tamaki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakao
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D000071178:CD48 Antigen; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy / Q000379:methods; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C000604066:Cd48 protein, mouse