title: Anti-CD138-targeted interferon is a potent therapeutic against multiple myeloma.
abstract: 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.
authors.affiliation: 1 Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles , Los Angeles, California.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Yoo
authors.forename: Kham R
authors.initials: KR
authors.lastname: Trinh
authors.forename: Danh
authors.initials: D
authors.lastname: Tran
authors.forename: Alex
authors.initials: A
authors.lastname: Vasuthasawat
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Bao
authors.initials: B
authors.lastname: Hoang
authors.forename: Alan
authors.initials: A
authors.lastname: Lichtenstein
authors.forename: Sherie L
authors.initials: SL
authors.lastname: Morrison
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy*; D015398:Signal Transduction; D053668:Syndecan-1 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D053668:Syndecan-1; D007372:Interferons