Bender H, Takahashi H, Adachi K, Belser P, Liang S H, Prewett M, Schrappe M, Sutter A, Rodeck U, Herlyn D
Wistar Institute, Philadelphia, Pennsylvania 19104.
Cancer Res. 1992 Jan 1;52(1):121-6.
Monoclonal antibody (mAb) 425 (IgG2a) binds to the external domain of the epidermal growth factor receptor. This determinant is highly expressed by human glioma tissues but rarely by normal brain tissues, and is absent on peripheral blood lymphocytes and bone marrow cells. The mAb exerts variable cytotoxic effects against cultured human glioma cells in conjunction with human and murine effector cells. Inhibition of growth of s.c. glioma xenografts in nude mice by the mAb may be mediated by murine macrophages or may be related to the capacity of the mAb to antagonize growth stimulation of glioma cells by epidermal growth factor. In approaches to radioimmunotherapy of human glioma with mAb 425, the 125I-labeled mAb 425 exhibited more significant antitumor effects than the 131I-labeled mAb both in vitro and in vivo in xenotransplanted nude mice. These differences may be due to enhanced nuclear damage caused by 125I-labeled versus 131I-labeled fragments following their internalization into the glioma cells. Our studies provide the rationale for immunotherapy of glioma patients with either unlabeled or 125I-labeled anti-epidermal growth factor receptor mAb 425.
单克隆抗体（mAb）425（IgG2a）与表皮生长因子受体的胞外结构域结合。这种决定簇在人胶质瘤组织中高度表达，而在正常脑组织中很少表达，在外周血淋巴细胞和骨髓细胞中不存在。该单克隆抗体与人和鼠的效应细胞共同作用，对培养的人胶质瘤细胞产生不同程度的细胞毒性作用。单克隆抗体对裸鼠皮下胶质瘤异种移植物生长的抑制作用可能由鼠巨噬细胞介导，也可能与单克隆抗体拮抗表皮生长因子对胶质瘤细胞生长刺激的能力有关。在用mAb 425进行人胶质瘤放射免疫治疗的方法中，125I标记的mAb 425在体外和体内异种移植裸鼠中均比131I标记的mAb表现出更显著的抗肿瘤作用。这些差异可能是由于125I标记的片段与131I标记的片段内化进入胶质瘤细胞后，前者导致的核损伤增强。我们的研究为用未标记或125I标记的抗表皮生长因子受体单克隆抗体425对胶质瘤患者进行免疫治疗提供了理论依据。
