Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen.
Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen.
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发表时间：
1998-10
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通讯作者：
M. Pride;S. Shuey;A. Grillo‐López;G. Braslawsky;M. Ross;S. Legha;O. Eton;A. Buzaid;C. Ioannides;J. Murray
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作者：
M. Pride;S. Shuey;A. Grillo‐López;G. Braslawsky;M. Ross;S. Legha;O. Eton;A. Buzaid;C. Ioannides;J. Murray
本研究的目的是确定两种模拟大多数黑色素瘤肿瘤上发现的高分子量蛋白聚糖抗原的抗独特型抗体的组合是否能够增强接种疫苗的高风险黑色素瘤患者的细胞免疫。使用两种免疫方案，用可变浓度的MELIMMUNE-1和MELIMMUNE-2的混合物，沿着佐剂SAF-m，免疫28名患有黑素瘤的I-IV期高风险患者。在第一次免疫前和最后一次免疫后4周收集外周血单核细胞，并测试对MELIMMUNE-1和MELIMMUNE-2的体外增殖以及对51 Cr标记的靶细胞系的细胞毒性。此外，测试来自体外增殖培养物的上清液的白细胞介素10和IFN-γ水平。在免疫后样品中观察到MELIMMUNE-1和MELIMMUNE-2的显著体外增殖，但在接种前样品中未观察到。MELIMMUNE-2的平均刺激指数（33.7 +/-0.6）显著高于MELIMMUNE-1的平均刺激指数（13.9 +/-0.3; P < 0.025）。从接种前或接种后78%的体外刺激培养物中获得的上清液含有显著水平的白细胞介素10（范围，0.43-142 pg/ml），而IFN-γ水平在53%的接种后样品中升高（范围，3-245 pg/ml），但在接种前样品中没有升高。更重要的是，我们能够在43%的患者中产生特异性CTL应答，这与IFN-γ水平升高相关。这些结果表明，MELIMMUNE增强了黑色素瘤患者的细胞介导的免疫力。
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.