Potent in vitro and in vivo effects of polyclonal anti-human-myeloma globulins

• Published in: Oncotarget Vol. 7; no. 41; pp. 67061 - 67070
• Main Authors: Schieferdecker, Aneta, Shoshani, Ofer, Westner, Benedikt, Zipori, Dov, Fehse, Boris, Kröger, Nicolaus, Ayuk, Francis
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 11.10.2016
• Subjects: Animals; Antibody-Dependent Cell Cytotoxicity - drug effects; Antilymphocyte Serum - pharmacology; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Multiple Myeloma; Research Paper; Xenograft Model Antitumor Assays; anti-human-myeloma globulins; myeloma; AMG; ATG; polyclonal antibodies
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.11489

Multiple myeloma is still incurable in most cases. Polyclonal anti T lymphocyte globulins (ATG) have been reported to kill human myeloma cells in vitro and in mouse models. Anti-human-myeloma globulins (AMG) were produced by immunizing rabbits with human myeloma cell lines RPMI-8226 (AMG-8226) or KMS-12-BM (AMG-12-BM). Cytotoxicity of the polyclonal antibodies was analyzed in vitro and in a xenograft NOD-SCID mouse model. Both AMG had stronger cytotoxicity against myeloma cells compared to ATG. In primary T cells, AMG-8226 showed greater complement-dependent cytotoxicity (CDC) than ATG, whereas complement-independent cytotoxicity did not differ. Effects on non-hematopoietic cell lines were also similar. Competitive blocking assays revealed fourfold more antibodies against CD38 in AMG-8226 compared to ATG. Low concentrations of AMG-8226 and ATG increased ADCC. At higher concentrations, ATG inhibited ADCC more potently than AMG-8226. Combinations of ATG and AMG-8226 with melphalan or bortezomib showed additive to synergistic cytotoxicity on myeloma cells. The cytotoxic effects of AMG and ATG were confirmed in the xenograft NOD-SCID mouse model. Our data show more potent antimyeloma effects of AMG compared to ATG. These results lay the ground for the development of polyclonal antibodies for the treatment of multiple myeloma.