Immunologic response to the dual murine anti-Id vaccine Melimmune-1 and Melimmune-2 in patients with high-risk melanoma without evidence of systemic disease.

Melimmune is a dual preparation of two murine anti-idiotypic antibodies (anti-Ids), Melimmune-1 and Melimmune-2, which mimic separate epitopes of the melanoma-associated high molecular weight proteoglycan antigen. In an animal model, vaccination with either anti-Id leads to tumor rejection, and Phase I clinical trials have demonstrated the tolerance of each reagent in humans. We conducted a Phase IB trial of different doses of a one-to-one composition to Melimmune-1 and Melimmune-2 administered with SAF-m adjuvant in patients with resected melanoma without evidence of metastatic disease. A total of 21 patients were enrolled in this multicenter trial. Detailed immune response analysis was conducted on 13 patients enrolled at a single institution. Following vaccination, 12 of the 13 patients demonstrated antibodies to both Melimmune-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 microgram/ml was detected in 4 and 10 of 12 patients, respectively. Sera from patients obtained at time of peak anti-V-region reactivity did not demonstrate the ability to inhibit Ab1 binding to tumor cells or direct anti-tumor cell reactivity. However, in vitro cellular proliferation was observed in response to Melimmune-1 and/or Melimmune-2 F(Ab')2 in all patients with a mean stimulation index of 12.0 and 27.8, respectively. Overall, the antibody and cellular immune response to Melimmune-2 was more potent than to Melimmune-1, and all antibody doses elicited an immune response. The optimal biologic dose of Melimmune could not be determined in this small patient population.

RCT Entities:   Population Interventions Outcomes