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.