The therapeutic efficacy of an anti-IL-2 receptor monoclonal antibody correlates with an increase in serum soluble IL-2 receptor levels.
We tested the capacity of three rat monoclonal antibodies (MoAb), recognizing different epitopes on the L chain of mouse interleukin-2 receptor (IL-2R), to block delayed-type hypersensitivity (DTH) and local graft-versus-host reaction (GVHR). Furthermore, we investigated the effect of IL-2R-targeted immunotherapy on serum soluble IL-2R levels by ELISA technique. Following administration of AMT-13 MoAb, in sufficient amounts to suppress both DTH (60-90% inhibition) and local GVHR (55-70% inhibition), an increase in soluble IL-2R levels up to 12-fold was observed. In contrast, the administration of 7D4 MoAb did not show any immunosuppressive effect in vivo and even decreased the soluble IL-2R levels. The third anti-IL-2R MoAb AMT45-20 had an intermediate effect. AMT45-20 MoAb marginally suppressed the DTH as well as local GVHR (15-35% inhibition) and induced only a slight increase in soluble IL-2R levels (up to 4-fold). Both cyclosporin A, a conventional immunosuppressive drug, and the anti-L3T4 MoAb, which defines the entire T helper cell subset, suppressed GVH and DTH response but did not increase the soluble IL-2R serum levels. The increased concentration of soluble IL-2R in the serum of successfully treated mice may be due to destruction of IL-2R-positive cells by anti-IL-2R-targeted immunotherapy and seems to be a sensitive indicator for the success of such a therapy.
Volk
H D
HD
Institut of Medical Immunology, Charité, Humboldt-Universität, Berlin, FRG.
Josimovic-Alasevic
O
O
Gross
M
M
Diamantstein
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D006087:Graft vs Host Reaction; D006968:Hypersensitivity, Delayed / Q000517:prevention & control*; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology*; D012995:Solubility
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2