Anti-CD138-targeted interferon is a potent therapeutic against multiple myeloma

Multiple myeloma (MM), a plasma cell malignancy, is the second most prevalent hematologic malignancy in the US. Although much effort has been made trying to understand the etiology and the complexities of this disease with the hope of developing effective therapies, MM remains incurable at this time...

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Veröffentlicht in:Journal of interferon & cytokine research 2015-04, Vol.35 (4), p.281-291
Hauptverfasser: Yoo, Esther M, Trinh, Kham R, Tran, Danh, Vasuthasawat, Alex, Zhang, Juan, Hoang, Bao, Lichtenstein, Alan, Morrison, Sherie L
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container_end_page 291
container_issue 4
container_start_page 281
container_title Journal of interferon & cytokine research
container_volume 35
creator Yoo, Esther M
Trinh, Kham R
Tran, Danh
Vasuthasawat, Alex
Zhang, Juan
Hoang, Bao
Lichtenstein, Alan
Morrison, Sherie L
description Multiple myeloma (MM), a plasma cell malignancy, is the second most prevalent hematologic malignancy in the US. Although much effort has been made trying to understand the etiology and the complexities of this disease with the hope of developing effective therapies, MM remains incurable at this time. Because of their antiproliferative and proapoptotic activities, interferons (IFNs) have been used to treat various malignancies, including MM. Although some success has been observed, the inherent toxicities of IFNs limit their efficacy. To address this problem, we produced anti-CD138 antibody fusion proteins containing either IFNα2 or a mutant IFNα2 (IFNα2(YNS)) with the goal of targeting IFN to CD138-expressing cells, thereby achieving effective IFN concentrations at the site of the tumor in the absence of toxicity. The fusion proteins inhibited the proliferation and induced apoptosis of U266, ANBL-6, NCI-H929, and MM1-144 MM cell lines. The fusion proteins decreased the expression of IFN regulatory factor 4 (IRF4) in U266. In addition, the fusion proteins were effective against primary cells from MM patients, and treatment with fusion proteins prolonged survival in the U266 murine model of MM. These studies show that IFNα antibody fusion proteins can be effective novel therapeutics for the treatment of MM.
doi_str_mv 10.1089/jir.2014.0125
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subjects Animals
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis - drug effects
Cell Proliferation - drug effects
Disease Models, Animal
Humans
Interferons - pharmacology
Interferons - therapeutic use
Mice
Multiple Myeloma - drug therapy
Research Reports
Signal Transduction
Syndecan-1 - immunology
title Anti-CD138-targeted interferon is a potent therapeutic against multiple myeloma
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