2013
DOI: 10.1016/j.ccr.2013.02.026
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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… Show more

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Cited by 65 publications
(67 citation statements)
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“…The potential benefit of targeting multiple myeloma tumor cells by specific mAbs alone or in combination with other antimultiple myeloma agents has also been demonstrated by other recent experimental and clinical studies (4,(20)(21)(22)(23)(24)(25)(26). For instance, bortezomib was described to synergistically enhance the lysis of ADCC mediated by the CS1 mAb elotuzumab in vitro (27).…”
Section: Discussionmentioning
confidence: 84%
“…The potential benefit of targeting multiple myeloma tumor cells by specific mAbs alone or in combination with other antimultiple myeloma agents has also been demonstrated by other recent experimental and clinical studies (4,(20)(21)(22)(23)(24)(25)(26). For instance, bortezomib was described to synergistically enhance the lysis of ADCC mediated by the CS1 mAb elotuzumab in vitro (27).…”
Section: Discussionmentioning
confidence: 84%
“…10.1 (anti-FcgR1) was a gift from Nancy Hogg (London Research Institute, Cancer Research UK, London, UK); E05 (anti-FcgRIIa) and 6G11 (anti-FcgRIIb) with Fc regions mutated to eliminate FcgR binding were produced by BioInvent International AB (Malmo, Sweden) by using phage display technology 11 TGN1412 was produced by using published sequences (US patent number US7585960). Variable regions were subcloned into expression vectors (pEE6.4 heavy chain and pEE12.4 light chain; Lonza) containing constant regions of human IgG4.…”
Section: Antibodiesmentioning
confidence: 99%
“…BI-505 binds to intercellular adhesion molecule-1 (ICAM-1), suggesting a previously unrecognized role for this receptor as a therapeutic target in cancer. The BI-505 epitope is strongly expressed on the surface of multiple myeloma cells from both newly diagnosed and relapsed patients (5). BI-505 has potent macrophage-dependent anti-myeloma activity.…”
Section: Introductionmentioning
confidence: 99%
“…BI-505 has potent macrophage-dependent anti-myeloma activity. It has been shown to enhance survival in advanced disseminated murine models of myeloma compared with currently used treatments, and to inhibit primary myeloma cell growth and bone damage in an SCID-hu model when used in combination with lenalidomide and bortezomib (5).…”
Section: Introductionmentioning
confidence: 99%
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