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Biological and immunological characterization of ATG and ALG
EL Raefsky, P Gascon, A Gratwohl, B Speck and NS Young
Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are
effective therapies in aplastic anemia; their mechanism of action is
undefined. We assayed multiple properties of ATG and ALG to address the
biological and immunological bases for differences between ATG and ALG and
lot variation. In addition, we studied a lot reported to be inactive in an
American clinical trial; however in retrospect, this lot appeared to be
active in patients treated in Europe. Immunoprecipitation of thymocyte and
lymphocyte membrane proteins with ATG and ALG showed between 14 and 18
major bands on SDS-PAGE, but the patterns for ATG and ALG were not
identical. The ability of ATG and ALG to block binding of labeled
monoclonal antibodies was assessed using flow cytometry and a
radioimmunoassay. In general, there was more lot variation among ALGs than
ATGs; however, all ALG lots were more potent blockers of binding of
anti-HLA-DR and anti-Leu 1 antibodies than was ATG. Both ALG and ATG
effectively blocked binding of anti-Leu 2a, anti- Leu 3a, anti-Leu 4,
anti-Leu 5b, and anti-IL 2 receptor abs; neither blocked binding of
anti-Leu 7. All preparations were capable of inducing T-cell blastogenesis,
although there was considerable lot variation. All lots lysed 60% to 75% T
cells in a rabbit complement- mediated cytotoxicity assay, with most having
a plateau of activity at 5 to 10 ug/mL. Two lots of ALG, including the lot
reported to be clinically inactive, showed less toxicity at suboptimal
concentrations and did not plateau even at 80 ug/mL. In total, these
results indicate important differences between ATG and ALG in general, more
lot variation among ALGs than ATGs and only differences in cytotoxicity
between an "inactive" lot of ALG and most, but not all, other active ATG
and ALG preparations.
Volume 68,
Issue 3,
pp. 712-719,
09/01/1986
Copyright © 1986 by The American Society of Hematology
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