Human monoclonal antibody against human, malignant glioma obtained from mouse-human hetero hybridoma system

针对恶性脑肿瘤的肿瘤特异性治疗或诊断方式是减少周围正常组织损伤的必要条件。在这个意义上，单克隆抗体应该是有用的。迄今为止，大多数单克隆抗体都是在小鼠-小鼠杂交瘤系统中制备的。为了临床使用，抗人恶性肿瘤的人免疫球蛋白是必需的。本研究从小鼠骨髓瘤细胞（P3Ul）和人外周血淋巴细胞之间的杂交瘤细胞系中获得了几种人免疫球蛋白G （IgG）。PAP免疫组化分析显示，其中10种人igg对5种不同的人胶质瘤有良好的反应，但对2种人髓母细胞瘤和1种转移性脑瘤完全没有反应。然而，过氧酶标记的抗人IgG作为第二抗体，与人胶质瘤细胞交叉。为了避免这种交叉反应，在使用抗人胶质瘤IgG和过氧酶标记的抗人IgG之前加入抗人IgG。这种预处理很好地阻断了胶质瘤细胞和b细胞之间的交叉反应性。结论：从小鼠-人异杂交瘤系统中获得了10个抗胶质瘤IgG。有几个问题需要解决，包括去除含有胎牛血清的培养基，进一步纯化和更多的肿瘤组和/或正常组织的特异性研究。

Tumor specific treatment or diagnostic modalities against malignant brain-tumor are necessary to decrease the surrounding normal tissue damage. In this meaning, monoclonal antibody should be useful. Up to date, most of the monoclonal antibodies have been made of mouse-mouse hybridoma system. For the purpose of clinical use, human immunoglobulin against human malignant tumor is necessary. In this investigation, several human immunoglobulin G (IgG) were obtained from hybridoma cell lines between mouse myeloma cells (P3Ul) and human peripheral blood lymphocytes. Ten of these human IgGs, showed well response with 5 different human glioma but did not respond with 2 human medulloblastomas and one metastatic brain tumor at all under PAP immunohistochemical analysis. However, peroxydase-labeled anti-human IgG, used as the second antibody, crossed with human glioma cells.To avoid this cross-reactivity, anti-human IgG was added before the use of antihuman-glioma IgG and peroxydase-labeled anti-human IgG. This pretreatment well blocked the cross-reactivity between glioma cells and B-cells. In conclusion, ten anti-human-glioma IgG were obtained from mouse-human heterohybridoma system. There are several problems to be solved, including removal of fetal calf serum containing in the culture medium, further purification and more investigation about specificity using much more tumor panel and/or normal tissues.