IMMUNOLOGICAL RESPONSE TO THE DUAL MURINE ANTI-ID VACCINE MELIMMUNE-1AND MELIMMUNE-2 IN PATIENTS WITH HIGH-RISK MELANOMA WITHOUT EVIDENCE OF SYSTEMIC-DISEASE

Melimmune is a dual preparation of two murine anti-idiotypic antibodie s (anti-Ids), Melimmune-1 and Melimmune-2, which mimic separate epitop es of the melanoma-associated high molecular weight proteoglycan antig en. Ln an animal model, vaccination with either anti-id leads to tumor rejection, and Phase I clinical trials have demonstrated the toleranc e of each reagent in humans. We conducted a Phase LB trial of differen t doses of a one-to-one composition of Melimmune-1 and Melimmune-2 adm inistered with SAF-m adjuvant in patients with resected melanoma witho ut evidence of metastatic disease. A total of 21 patients were enrolle d in this multicenter trial. Detailed immune response analysis was con ducted on 13 patients enrolled at a single institution. Following vacc ination, 12 of the 13 patients demonstrated antibodies to both Melimmu ne-1 and Melimmune-2, including significant anti-V-region reactivity. Maximum anti-V-region reactivity was generally detected following the last vaccination. Anti-V-region reactivity directed at Melimmune-1 and Melimmune-2 in excess of 1 mu g/ml was detected in 4 and 10 of 12 pat ients, respectively. Sera from patients obtained at time of peak anti- V-region reactivity did not demonstrate the ability to inhibit Abl bin ding to tumor cells or direct anti-tumor cell reactivity. However, in vitro cellular proliferation was observed in response to Melimmune-1 a nd/or Melimmune-2 F(Ab')(2) in all patients with a mean stimulation in dex of 12.0 and 27.8, respectively. Overall, the antibody and cellular immune response to Melimmune-2 was more potent than to Melimmune-1, a nd all antibody doses elicited an immune response. The optimal biologi c dose of Melimmune could not be determined in this small patient popu lation.