SYNERGY BETWEEN AN ANTIBODY AND CD8(+) CELLS IN ELIMINATING AN ESTABLISHED TUMOR

We investigated the effector mechanisms operating during the rejection of a transplantable solid lymphoma E.G7 (H-2(b)) which expresses the gene encoding chicken ovalbumin (OVA). Anti-OVA cytotoxic T lymphocyte s (CTL) completely and specifically protected animals from the onset o f, but could not eradicate established, E.G7 tumors. The growth of the same lymphoma was also effectively prevented by the antibody GK1.5, w hose target molecule, CD4, was expressed on E.G7 cells in vivo. Furthe rmore, GK1.5 was able to eradicate established solid E.G7 tumors. GK1. 5-mediated tumor elimination was due to its antitumor activity, and no t to the elimination of regulatory CD4(+) cells, based on unimpaired t umor growth in the absence of GK1.5 in animals that genetically lack C D4 T cells. In vitro, GK1.5 did not kill tumor cells: complement activ ation or apoptosis induction were not evident. In vivo, GK1.5-mediated tumor regression did not depend on natural killer cells, but it absol utely required CD8(+) cells and intact Fc gamma receptor. We conclude that, in the E.G7 model, the collaboration of antibody and CTL immunit y was crucial for the successful immunotherapy of established tumors. The mechanism of this collaboration is discussed.