Effector mechanism in antitumor activity of monoclonal antibodies produced against an ascitic mouse mammary tumor.
Therapeutic effects of monoclonal antibodies with different immunoglobulin classes, detecting the same antigenic determinant of tumor specific antigen expressed on ascitic mouse mammary tumor MM46, were examined. With i.v. administration of gamma 2a, gamma 2b, or gamma 1 antibody we were able to keep a significant proportion of mice tumor free against i.p. inoculation of 5 X 10(4) MM46 cells with doses as small as 0.5 micrograms, but with administration of mu, gamma 3, or alpha antibody we were not able to keep mice tumor free with doses up to 5 micrograms. With 200 micrograms of antibody, however, an antitumor effect was observed even with mu or gamma 3 antibody, although alpha antibody still showed no effect at all. The therapeutic effect of gamma 2a was further examined in mice challenged with an increasing dose of tumor cells, and a significant effect was demonstrated against 1 X 10(6) cells with 200 micrograms of antibody but not against 5 X 10(6) cells. To assess the effector cells in antitumor activity of antibody in vivo, a histological examination of the tumor cells treated with each class of antibody was carried out. The tumor treated by gamma 2a antibody revealed a remarkable cell infiltration consisting predominantly of mononuclear cells, whereas those treated by mu, gamma 3, or alpha antibody did not. The tumor cells treated by gamma 1 or gamma 2b antibody showed a moderate cellular reaction. Next, a Winn assay was carried out in athymic C3H/HeN-nu/nu mice using gamma 2a antibody. A significant antitumor effect was observed even in those mice, indicating that T-cells are not predominant effector cells. The role of macrophages was studied in mice treated with two macrophage toxic agents, carrageenan and silica particles. These agents were shown to reduce the antitumor effect of gamma 2a antibody in both Winn assays and therapeutic experiments. Thus, histological examination and the blocking effect of macrophage toxic agents suggested the participation of host macrophages as effector cells in antibody-mediated tumor cell suppression in vivo.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002351:Carrageenan / Q000494:pharmacology; D007136:Immunoglobulins / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D012822:Silicon Dioxide / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D012822:Silicon Dioxide; D002351:Carrageenan