Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen.

Abstract

The purpose of this study was to determine whether a combination of two anti-idiotypic antibodies that mimic the high molecular weight proteoglycan antigen found on most melanoma tumors was capable of enhancing cellular immunity in vaccinated high-risk patients with melanoma. Twenty-eight stage I-IV high-risk patients with melanoma were immunized with a mixture of variable concentrations of MELIMMUNE-1 and MELIMMUNE-2, along with the adjuvant SAF-m, using two immunization schedules. Peripheral blood mononuclear cells were collected before the first immunization and 4 weeks after the final immunization and tested for in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 and for cytotoxicity against 51Cr-labeled target cell lines. Additionally, supernatants from in vitro proliferation cultures were tested for interleukin 10 and IFN-gamma levels. Significant in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 were observed in postimmunization samples but not in prevaccination samples. The mean stimulation index for MELIMMUNE-2 (33.7 +/- 0.6) was significantly higher than that for MELIMMUNE-1 (13.9 +/- 0.3; P < 0.025). Supernatants obtained from 78% of the in vitro stimulated cultures pre- or postvaccination contained significant levels of interleukin 10 (range, 0.43-142 pg/ml), whereas IFN-gamma levels were elevated in 53% of postvaccination samples (range, 3-245 pg/ml) but not prevaccination samples. More importantly, we were able to generate specific CTL responses in 43% of the patients, which correlated with elevated IFN-gamma levels. These results indicate that MELIMMUNE enhances cell-mediated immunity in patients with melanoma.

• Authors: M W Pride, S Shuey, A Grillo-Lopez, G Braslawsky, M Ross, S S Legha, O Eton, A Buzaid, C Ioannides, J L Murray
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 4 Issue 10 Pg. 2363-70 (Oct 1998) ISSN: 1078-0432 [Print] United States
• PMID: 9796966 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Monoclonal
• Antigens, Neoplasm
• Cytokines
• HLA-A2 Antigen
• Melanoma-Specific Antigens
• Neoplasm Proteins
• Proteoglycans

Topics

• Antibodies, Anti-Idiotypic (immunology)
• Antibodies, Monoclonal (immunology)
• Antigens, Neoplasm (immunology)
• Cytokines (blood)
• HLA-A2 Antigen (analysis)
• Humans
• Immunization
• Lymphocyte Activation
• Melanoma (immunology)
• Melanoma-Specific Antigens
• Molecular Weight
• Neoplasm Proteins (immunology)
• Proteoglycans (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured