Complement-dependent and complement-independent cytotoxicity of polyclonal antithymocyte globulins in chronic lymphocytic leukemia.
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Complement-dependent and complement-independent cytotoxicity of polyclonal antithymocyte globulins in chronic lymphocytic leukemia. / Ayuketang Ayuk, Francis; Atassi, Nabil; Schuch, Gunter; Mina, Sormeh; Fang, Lubin; Bokemeyer, Carsten; Fehse, Boris; Zander, Axel R.; Kröger, Nicolaus.
in: LEUKEMIA RES, Jahrgang 32, Nr. 8, 8, 2008, S. 1200-1206.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Complement-dependent and complement-independent cytotoxicity of polyclonal antithymocyte globulins in chronic lymphocytic leukemia.
AU - Ayuketang Ayuk, Francis
AU - Atassi, Nabil
AU - Schuch, Gunter
AU - Mina, Sormeh
AU - Fang, Lubin
AU - Bokemeyer, Carsten
AU - Fehse, Boris
AU - Zander, Axel R.
AU - Kröger, Nicolaus
PY - 2008
Y1 - 2008
N2 - OBJECTIVE: Despite important progress in its management, chronic lymphocytic leukemia (CLL) remains incurable with standard therapies. Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients with CLL. Polyclonal antithymocyte (or anti-T-cell) globulins (ATGs) are used for conditioning in allogeneic SCT mainly due to their anti-T-cell activity. ATGs however, contain antibodies targeting antigens expressed on various hematopoietic cells including B cells. METHODS: We assessed anti-CLL activity of two commercially available ATG preparations at clinically relevant concentrations (10-100 microg/ml) in CLL samples from 16 patients. Cytotoxicity was determined by staining with 7-amino-actinomycin D (7-AAD), annexin V and flow cytometry. RESULTS: Both ATG preparations induced marked complement-independent dose-dependent cytotoxicity in all samples. Addition of complement strongly enhanced the cytotoxic effect of both ATG preparations significantly. ATG-induced complement-dependent cytotoxicity (CDC) was at least as high as that observed with Alemtuzumab. Both ATGs enhanced the cytotoxic effect of Fludarabine. CONCLUSION: ATG is an effective agent against CLL in vitro. We suggest that this potential be taken into consideration when developing stem cell transplantation protocols for patients with CLL.
AB - OBJECTIVE: Despite important progress in its management, chronic lymphocytic leukemia (CLL) remains incurable with standard therapies. Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients with CLL. Polyclonal antithymocyte (or anti-T-cell) globulins (ATGs) are used for conditioning in allogeneic SCT mainly due to their anti-T-cell activity. ATGs however, contain antibodies targeting antigens expressed on various hematopoietic cells including B cells. METHODS: We assessed anti-CLL activity of two commercially available ATG preparations at clinically relevant concentrations (10-100 microg/ml) in CLL samples from 16 patients. Cytotoxicity was determined by staining with 7-amino-actinomycin D (7-AAD), annexin V and flow cytometry. RESULTS: Both ATG preparations induced marked complement-independent dose-dependent cytotoxicity in all samples. Addition of complement strongly enhanced the cytotoxic effect of both ATG preparations significantly. ATG-induced complement-dependent cytotoxicity (CDC) was at least as high as that observed with Alemtuzumab. Both ATGs enhanced the cytotoxic effect of Fludarabine. CONCLUSION: ATG is an effective agent against CLL in vitro. We suggest that this potential be taken into consideration when developing stem cell transplantation protocols for patients with CLL.
M3 - SCORING: Zeitschriftenaufsatz
VL - 32
SP - 1200
EP - 1206
JO - LEUKEMIA RES
JF - LEUKEMIA RES
SN - 0145-2126
IS - 8
M1 - 8
ER -
