Complement-dependent and complement-independent cytotoxicity of polyclonal antithymocyte globulins in chronic lymphocytic leukemia.
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.


CONCLUSIONS
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.
Ayuk
Francis A
FA
Department of Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. ayuketan@uke.uni-hamburg.de
Atassi
Nabil
N
Schuch
Gunther
G
Mina
Sormeh
S
Fang
Lubin
L
Bokemeyer
Carsten
C
Fehse
Boris
B
Zander
Axel R
AR
Kröger
Nicolaus
N
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D003165:Complement System Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D000074323:Alemtuzumab; D003165:Complement System Proteins