ANTIIDIOTYPE VACCINE WITH IL2 FOR ADVANCED MELANOMA

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DESCRIPTION (Applicant's Description) We have generated an anti-idiotype antibody, 1A7, that is the internal image of the GD2 disialoganglioside. We have demonstrated in a preliminary trial that 100 percent of patients with metastatic melanoma will generate an active immune response against GD2 following adequate immunization with the 1A7 anti-idiotype antibody mixed with 100mcg of QS-21 adjuvant. We demonstrated a polyclonal humoral immune response with specific binding to purified GD2 disialoganglioside and GD2 positive cells, that mediated antibody-dependent cellular cytotoxicity, and was predominately of the IgG isotype. While none of the patients had objective clinical responses to 1A7, three of the first seven continue on vaccine with stable disease from 14-26+ months. Toxicity was limited to local reactions at the site of the injection with occasional mild fevers. Low dose daily subcutaneous IL-2 has minimal toxicity and can expand several fold in vivo peripheral blood NK cells in the daily dose range from 0.4 to 1.5 x 106 international units per meter squared of IL-2. To stimulate the cytotoxic mechanism, pulse doses of intermediate dose level IL-2 at 1.5 million international units per meter squared were given for three consecutive days every two weeks. NK cells express Fc receptors and participate in antibody dependent cellular cytotoxicity. In principle, antibodies capable of binding both tumor targets and peripheral blood mononuclear cells could deliver effector cells to primary tumor sites as well as augment cytotoxicity. In this study, we propose to combine low dose IL2 with the 1A7 anti-idiotype antibody. This will be a feasibility trial with ten patients treated on each of the three arms. The specific aims of this trial will be to determine the best immune response achieved by the three schedules of 1A7 and IL-2. Additional specific aims of the study will be to determine toxicities and clinical responses.