Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen.
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.
Pride
M W
MW
Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Shuey
S
S
Grillo-Lopez
A
A
Braslawsky
G
G
Ross
M
M
Legha
S S
SS
Eton
O
O
Buzaid
A
A
Ioannides
C
C
Murray
J L
JL
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology*; D011509:Proteoglycans / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D016207:Cytokines; D015789:HLA-A2 Antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011509:Proteoglycans