title: Potent in vitro and in vivo effects of polyclonal anti-human-myeloma globulins.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Current Affiliation: Department of Oncology and Hematology with Section Pneumology, Hubertus Wald Tumorzentrum/ UCCH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Aneta
authors: A
authors: Schieferdecker
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.|Current Affiliation: San Diego Branch, Ludwig Institute for Cancer Research, La Jolla, CA, USA.
authors: Ofer
authors: O
authors: Shoshani
authors: Neovii (formerly Fresenius) Biotech GmbH, Gräfelfing, Germany.|Current Affiliation: Acino AG, Miesbach, Germany.
authors: Benedikt
authors: B
authors: Westner
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors: Dov
authors: D
authors: Zipori
authors: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Boris
authors: B
authors: Fehse
authors: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Nicolaus
authors: N
authors: Kröger
authors: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Francis
authors: F
authors: Ayuk
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma; D023041:Xenograft Model Antitumor Assays
chemical_list: D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents
keywords: AMG; ATG; anti-human-myeloma globulins; myeloma; polyclonal antibodies