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.

Abstract

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.

• Authors: M N Saleh, D Y Lalisan Jr, M W Pride, A Solinger, M S Mayo, A F LoBuglio, J L Murray
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 21 Issue 5 Pg. 379-88 (Sep 1998) ISSN: 1524-9557 [Print] United States
• PMID: 9789200 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Neoplasm
• Antigens, Neoplasm
• Cancer Vaccines
• Epitopes
• Neoplasm Proteins
• Proteoglycans
• melanoma-associated proteoglycan antigen, human

Topics

• Adult
• Aged
• Animals
• Antibodies, Anti-Idiotypic (immunology)
• Antibodies, Neoplasm (analysis)
• Antigens, Neoplasm (immunology)
• Cancer Vaccines (administration & dosage)
• Epitopes (immunology)
• Female
• Humans
• Immunity, Cellular (drug effects)
• Immunotherapy, Active
• Lymphocyte Activation (drug effects)
• Male
• Melanoma (drug therapy, immunology)
• Mice
• Middle Aged
• Neoplasm Proteins (immunology)
• Proteoglycans (immunology)