title: A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo.
abstract: We isolated a tumor B-cell-targeting antibody, BI-505, from a highly diversified human phage-antibody library, using a pioneering "function-first" approach involving screening for (1) specificity for a tumor B cell surface receptor, (2) induction of tumor programmed cell death, and (3) enhanced in vivo antitumor activity compared to currently used treatments. BI-505 bound to intercellular adhesion molecule-1, identifying a previously unrecognized role for this receptor as a therapeutic target in cancer. The BI-505 epitope was strongly expressed on the surface of multiple myeloma cells from both newly diagnosed and relapsed patients. BI-505 had potent macrophage-dependent antimyeloma activity and conferred enhanced survival compared to currently used treatments in advanced experimental models of multiple myeloma.
authors.affiliation: BioInvent International, Sölvegatan 41, 22370 Lund, Sweden.
authors.forename: Niina
authors.initials: N
authors.lastname: Veitonmäki
authors.forename: Markus
authors.initials: M
authors.lastname: Hansson
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Annika
authors.initials: A
authors.lastname: Sundberg
authors.forename: Tobias
authors.initials: T
authors.lastname: Löfstedt
authors.forename: Anne
authors.initials: A
authors.lastname: Ljungars
authors.forename: Zhan-Chun
authors.initials: ZC
authors.lastname: Li
authors.forename: Titti
authors.initials: T
authors.lastname: Martinsson-Niskanen
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.forename: Lena
authors.initials: L
authors.lastname: Danielsson
authors.forename: Mathilda
authors.initials: M
authors.lastname: Kovacek
authors.forename: Andrea
authors.initials: A
authors.lastname: Lundqvist
authors.forename: Linda
authors.initials: L
authors.lastname: Mårtensson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Teige
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Björn
authors.initials: B
authors.lastname: Frendéus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D019151:Peptide Library; D017452:Receptors, IgG / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D019151:Peptide Library; D017452:Receptors, IgG; D018799:Intercellular Adhesion Molecule-1