In vivo tumouricidal effects of LAD-1 monoclonal antibody on murine RL-male-1 lymphoma mediated by enhanced phagocytosis.
We have reported previously that the LAD-4 monoclonal antibody (mAb) directed against a fibronectin receptor (FNR) on RL-male-1 T lymphoma cells in BALB/c mice partially inhibited their migration to the liver. In the present study, we examined the mechanism by which another anti-FNR mAb, LAD-1, exerts its antitumourigenic effects. Administration of LAD-1 significantly prolonged survival of BALB/c mice challenged previously with RL-male-1 cells. LAD-1 enhanced phagocytosis of RL-male-1 cells by hepatic macrophages and clodronate-mediated macrophage depletion abrogated the antitumour activity of LAD-1. In vitro experiments revealed that a pan-caspase inhibitor, zVAD-fmk, did not affect the ability of LAD-1 to inhibit the proliferation of RL-male-1 cells. These data suggest that the antitumour effects of LAD-1 may be dependent on stimulation of tumour cell phagocytosis and are apoptosis-independent. Thus, LAD-1-induced phagocytosis of lymphoma cells by hepatic macrophages in mice may, at least in part, be responsible for the prolonged survival of the mice.
Ito
M
M
Molecular Biology and Retroviral Genetics Group, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Omoto
S
S
Kato
Y
Y
Hayashi
T
T
Mori
N
N
Fujii
Y R
YR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D008081:Liposomes; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010587:Phagocytosis / Q000276:immunology*; D011419:Propidium / Q000493:pharmacokinetics; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D008081:Liposomes; D016169:Lymphocyte Function-Associated Antigen-1; D011419:Propidium