Activation of mouse macrophages by muramyl dipeptide coupled with an anti-macrophage monoclonal antibody.
A rat IgG2a monoclonal antibody (mAb3A33) directed against the mouse Mac-1 antigen was conjugated with muramyl dipeptide (MDP) by using an intermediate polymer; under such conditions 75 MDP molecules were bound to one antibody molecule. A poly(L-lysine) polymer substituted with muramyl dipeptide and 3-(2-pyridyldithio)propionyl residues were prepared, the remaining lysine epsilon-amino groups were acylated with D-gluconolactone, leading to a neutral polymer; then a few polymer conjugates were coupled to mAb3A33 via a disulfide bridge. The binding capacity of the monoclonal antibody was preserved after conjugation with MDP-polymer molecules. Mouse peritoneal macrophages, incubated for 24 h with MDP-mAb3A33 conjugate became cytostatic against P815 mastocytoma cells, whereas unconjugated mAb3A33 and MDP-bound to a nonspecific rat IgG2a were ineffective. An enhancement of the cytostatic activity induced by MDP-mAb3A33 conjugate was obtained in the presence of gamma-IFN. These results show that several tens of MDP molecules can be linked to a macrophage-specific monoclonal antibody by using a neutral intermediate polymer without impairing the binding antibody capacity and that this type of MDP conjugate can efficiently activate macrophages and therefore could be the basis of the development of new antitumor therapy.
Midoux
P
P
Service d'Immunologie-Immunothérapie, Centre Régional de Lutte contre le Cancer, Rennes, France.
Martin
A
A
Collet
B
B
Monsigny
M
M
Roche
A C
AC
Toujas
L
L
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D011107:Polylysine / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D016177:Macrophage-1 Antigen; D011107:Polylysine; D000119:Acetylmuramyl-Alanyl-Isoglutamine