Takahashi T, Johnson T D, Nishinaka Y, Morton D L, Irie R F
Department of Biotechnology Sciences, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
J Invest Dermatol. 1999 Feb;112(2):205-9. doi: 10.1046/j.1523-1747.1999.00493.x.
Melanoma cells express ganglioside antigens GM3, GD3, GM2, and GD2 on their surface. This study examined whether immunization with a melanoma cell vaccine induced anti-ganglioside antibody responses in melanoma patients and whether these responses were correlated with survival. Sixty-six patients who had received melanoma cell vaccine immunotherapy after surgical removal of regional metastatic melanoma were identified. Cryopreserved serum samples from these patients were used in an enzyme-linked immunsorbent assay to determine the IgM antibody levels to GM2, GD2, GM3, and GD3 prior to melanoma cell vaccine treatment and 4 wk after the first melanoma cell vaccine immunization. All antibody levels significantly increased by week 4 (p < 0.001 for all four antibodies) and all increases were significantly associated with survival (anti-GD2, p < 0.001; anti-GM2, p = 0.001; anti-GD3, p < 0.001; anti-GM3, p < 0.001). Anti-tumor activity of these antibodies was proved using five representative antibody-positive sera in a complement-dependent cytotoxicity assay with cultured melanoma cell lines. These studies suggest that GM2, GD2, GM2, and GD3 expressed by melanoma cells can induce specific IgM antibodies and that high levels of these antibodies might have a beneficial impact on survival.
黑色素瘤细胞在其表面表达神经节苷脂抗原GM3、GD3、GM2和GD2。本研究检测了黑色素瘤细胞疫苗免疫接种是否能在黑色素瘤患者中诱导抗神经节苷脂抗体反应，以及这些反应是否与生存相关。确定了66例在手术切除区域转移性黑色素瘤后接受黑色素瘤细胞疫苗免疫治疗的患者。使用这些患者的冷冻保存血清样本，通过酶联免疫吸附测定法来确定黑色素瘤细胞疫苗治疗前以及首次黑色素瘤细胞疫苗免疫接种后4周时针对GM2、GD2、GM3和GD3的IgM抗体水平。到第4周时，所有抗体水平均显著升高（所有四种抗体的p<0.001），且所有升高均与生存显著相关（抗GD2，p<0.001；抗GM2，p = 0.001；抗GD3，p<0.001；抗GM3，p<0.001）。在与培养的黑色素瘤细胞系进行的补体依赖性细胞毒性试验中，使用五份具有代表性的抗体阳性血清证明了这些抗体的抗肿瘤活性。这些研究表明，黑色素瘤细胞表达的GM2、GD2、GM2和GD3可诱导特异性IgM抗体，且这些抗体的高水平可能对生存产生有益影响。
