ADMINISTRATION OF R24 MONOCLONAL-ANTIBODY AND LOW-DOSE INTERLEUKIN-2 FOR MALIGNANT-MELANOMA

R24 is a monoclonal antibody that recognizes the disialoganglioside G( D3) expressed on the surface of malignant melanoma cells, Once bound, it can mediate destruction of these cells through both complement-medi ated lysis and antibody-dependent cellular cytotoxicity. Agents such a s interleukin 2 (IL-2), which can augment effector cell function and p romote destruction of antibody-coated tumor cells, might produce impro ved antitumor responses when combined with R24, In this series, we eva luated the combination of R24 and IL-2 in a Phase Ib study in patients with metastatic melanoma, Twenty-eight patients with metastatic melan oma were entered into the protocol at two institutions, Patients recei ved 8 weeks of IL-2 by continuous i,v, infusion at a dose (4.5 x 10(5) Amgen units/m(2)/day) designed to selectively expand natural killer ( NK) cells, In weeks 5 and 6, patients received R24 for a total of four doses, Twenty-four h after each R24 infusion, patients received a 2-h bolus dose of IL-2 to help promote activity of NK effecters against a ntibody-coated melanoma targets, Additional IL-2 boluses were administ ered in weeks 7 and 8, Doses were escalated through two bolus doses of R24 (5 or 15 mg/m(2)) and two bolus doses of IL-2 (2.5 or 5.0 x 10(5) units/m(2)), Although one patient experienced severe capillary leak s yndrome during IL-2, therapy was otherwise well tolerated, At the high er dose level of R24, two of four patients experienced transient but s evere abdominal and chest discomfort, necessitating dose reduction, On e patient with ocular melanoma and liver metastases had a partial resp onse, Two additional patients had minor responses, A dramatic increase in NK cell number was noted as a result of treatment, as was augmenta tion of cytolytic activity against cultured NK-sensitive targets, Anti body-dependent cellular cytotoxicity against cultured melanoma cells i n the presence of exogenous R24 or in the presence of serum obtained f rom patients following R24 infusion also increased during treatment, O ur experience indicates that R24 and low-dose IL-2 can be safely combi ned in patients with metastatic melanoma and that this combination can promote destruction of cultured melanoma cells, The clinical activity of this combination against ocular melanoma may merit further investi gation.