The ability of lymphokine-activatedkiller (LAK) cells to mediate antibody-dependent cellular cytotoxicity and its efficacy against a LAX

The ability of lymphokine-activatedkiller (LAK) cells to mediate antibody-dependent cellular cytotoxicity and its efficacy against a LAX resistant tumor were investigated. Cells ofthe MH134 murine hepatoma line are scarcely lysed by LAX cells generated in vitro by incubatiOn of G3H/HeN mousespleen cells with humanrecombinantinterleukin2 (rIL 2). However, the splenic LAX cells potently lysed the LAX-resistant tumor cells in the presence of 11G2, a monoclonal antibody (MAb) of the IgGl Isotype reactive with a part of MM antigen. Peritoneal cells inducedby daily i.p. injectionsof rIL 2 not only exhibited LAX activity but also mediated antibody-dependent cellular cytotoxicity against MH134 tumor cells in the presence of 11G2. The peritoneal cells exhibiting these cytotoxic activities were found to be nonadherent and nonphagocyticmononuclearcells possessinga similar cell surface phe notype as that of splenic ZAK cells, that is Thy-1.2@, Lyt-1.1, Lyt 2.1, and asialo GM1'. Treatmentof spleen cells with antibodiesand complement before culture with rIL 2 revealed that the PhenOtypeof splenic LAX precursorsis Thy-1.2 and asialo GM,@.The in vii'o induction of peritoneal LAX cells in response to i.p. injections of rIL 2 was markedly depressed in C57BL/6 beige mice but was normally accom plished in BALB/c nude mice. Combined therapy of C3H/HeN mice bearing MH134 ascitic tumor with i.p. injection of rIL 2 and 11G2 brought about potent suppression of the tumor growth, resulting in the significant increase in the number of tumor-free mice, whereas neither rIL 2 nor the MAb couldexhibit such a potentantitumoreffect when used alone. Injection (i.v.) of anti-asialo GM1 antibody not only blocked the inductionof peritonealLAX cells by rIL 2 but also abrogatedthe development of the antitumor effect of the combined therapy. These results strongly suggest that combination of antitumor MAbs capable of inducing antibody-dependent cellular cytotoxicity with rIL 2 therapy could result in the generation of potent antitumor effects against LAX resistant tumors and that asialo GM3-positivenon-T-cell populations includingcells of the natural killer cell lineage are essential, at least in part, for development of the antitumor effects of the combined therapy with rIL 2 and MAbs.