Anti-Thymocyte Globulin (ATG) Induces Apoptosis in Myeloma Cells: A Basis for Myeloma Sero-Therapy?.

Allogeneic stem cell transplantation is a potentially curative therapy for patients with multiple myeloma. Polyclonal ATG is included in conditioning regimens to enhance engraftment and reduce the risk of severe graft-versus-host disease. Since ATG has been reported to induce depletion of T-, B- and dendritic cells, we sought to investigate its cytotoxic activity on myeloma cells. Complement-mediated and complement-independent activity of ATG-Fresenius was investigated on 4 myeloma cell lines (RPMI-8226, U266, KMS-12-BM and EJM) and bone marrow samples from 6 myeloma patients. Cytotoxicity was determined by staining with annexin V-FITC and 7AAD followed by flow cytometry. ATG at clinically relevant concentrations induced up to 100% and 85% complement-dependent killing of myeloma cell lines and primary myeloma samples respectively. In the absence of complement ATG still induced up to 50% and 80% apoptosis in myeloma cell lines and primary myeloma samples respectively. Preincubation of myeloma cells with a general caspase inhibitor (ZVAD-fmk) abrogated ATG-induced complement-independent cell death. Absorption assays indicate that ATG induced cytotoxicity is mediated by specific antibodies and antigens whose further elucidation may pave the way for antibody-based myeloma therapy.