Antithymocyte globulin induces complement-dependent cell lysis and caspase-dependent apoptosis in myeloma cells.

TY - JOUR

T1 - Antithymocyte globulin induces complement-dependent cell lysis and caspase-dependent apoptosis in myeloma cells.

AU - Ayuketang Ayuk, Francis

AU - Fang, Lubin

AU - Fehse, Boris

AU - Zander, Axel R

AU - Kröger, Nicolaus

PY - 2005

Y1 - 2005

N2 - OBJECTIVE: Allogeneic stem cell transplantation is a potentially curative therapy for patients with multiple myeloma. Polyclonal antithymocyte globulins (ATG) or monoclonal anti-CD52 (Alemtuzumab) are included in conditioning regimens to enhance engraftment and reduce risk of severe graft-vs-host disease. Because both agents have been reported to induce depletion of B cells, we sought to investigate their cytotoxic activity on myeloma cells. MATERIALS AND METHODS: Complement-mediated and complement-independent activity of ATG-Fresenius and Alemtuzumab was investigated on four myeloma cell lines (RPMI-8226, U266, KMS-12-BM, and EJM) and bone marrow samples from six myeloma patients. Cytotoxicity was determined by staining with annexin V-fluorescein isothiocyanate and 7-amino-actinomycin D followed by flow cytometry. RESULTS: ATG at a concentration of 500 microg mL(-1) 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 could induce up to 50% and 80% apoptosis in myeloma cell lines and primary myeloma samples, respectively. Preincubation of myeloma cells with a general caspase inhibitor abrogated ATG-induced complement-independent cell death. Alemtuzumab-mediated myeloma cytotoxicity was only observed in KMS-12-BM cells, and in none of the patient samples. CONCLUSION: ATG induces marked cytotoxic activity both in myeloma cell lines and in primary myeloma samples. Further elucidation of antibodies and antigens involved may pave the way for antibody-based myeloma therapy.

AB - OBJECTIVE: Allogeneic stem cell transplantation is a potentially curative therapy for patients with multiple myeloma. Polyclonal antithymocyte globulins (ATG) or monoclonal anti-CD52 (Alemtuzumab) are included in conditioning regimens to enhance engraftment and reduce risk of severe graft-vs-host disease. Because both agents have been reported to induce depletion of B cells, we sought to investigate their cytotoxic activity on myeloma cells. MATERIALS AND METHODS: Complement-mediated and complement-independent activity of ATG-Fresenius and Alemtuzumab was investigated on four myeloma cell lines (RPMI-8226, U266, KMS-12-BM, and EJM) and bone marrow samples from six myeloma patients. Cytotoxicity was determined by staining with annexin V-fluorescein isothiocyanate and 7-amino-actinomycin D followed by flow cytometry. RESULTS: ATG at a concentration of 500 microg mL(-1) 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 could induce up to 50% and 80% apoptosis in myeloma cell lines and primary myeloma samples, respectively. Preincubation of myeloma cells with a general caspase inhibitor abrogated ATG-induced complement-independent cell death. Alemtuzumab-mediated myeloma cytotoxicity was only observed in KMS-12-BM cells, and in none of the patient samples. CONCLUSION: ATG induces marked cytotoxic activity both in myeloma cell lines and in primary myeloma samples. Further elucidation of antibodies and antigens involved may pave the way for antibody-based myeloma therapy.

M3 - SCORING: Zeitschriftenaufsatz

VL - 33

SP - 1531

EP - 1536

JO - EXP HEMATOL

JF - EXP HEMATOL

SN - 0301-472X

IS - 12

M1 - 12

ER -