Mueller B M, Romerdahl C A, Trent J M, Reisfeld R A
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Cancer Res. 1991 Apr 15;51(8):2193-8.
The human melanoma cell line M24met metastasizes spontaneously from s.c. tumors to multiple distant sites in mice with severe combined immunodeficiency. Metastasis to lymph nodes and lungs is found in 100% of the animals. M24met has an undifferentiated phenotype and extra copies of the short arm of chromosome 7. This cell line expresses the epidermal growth factor receptor, and 425.3, a monoclonal antibody to the epidermal growth factor receptor, binds to 291,000 receptor molecules per M24met cell with a KD of 2.3 x 10(-10) M. This antibody has no effect on the proliferation of M24met cells under tissue culture conditions and does not mediate effector cell or complement-dependent cytotoxicity of these cells in vitro. However, treatment of established s.c. M24met tumors in mice with severe combined immunodeficiency with monoclonal antibody 425.3 specifically suppresses spontaneous metastasis of these tumors. Total doses of 4, 2, and 1 mg antibody per mouse decrease the number and size of melanoma metastases and prolong the life span of treated animals. Treatment with 4 mg of the F(ab')2 fragment of monoclonal antibody 425.3 does not influence M24met melanoma metastasis, implying a significant contribution of the Fc portion to the antimetastatic effect of this antibody.
人黑色素瘤细胞系M24met可从严重联合免疫缺陷小鼠的皮下肿瘤自发转移至多个远处部位。100%的动物会发生淋巴结和肺部转移。M24met具有未分化表型以及7号染色体短臂的额外拷贝。该细胞系表达表皮生长因子受体，针对表皮生长因子受体的单克隆抗体425.3以2.3×10⁻¹⁰ M的解离常数与每个M24met细胞上的291,000个受体分子结合。在组织培养条件下，该抗体对M24met细胞的增殖没有影响，并且在体外不介导这些细胞的效应细胞或补体依赖性细胞毒性。然而，用单克隆抗体425.3治疗严重联合免疫缺陷小鼠已形成的皮下M24met肿瘤，可特异性抑制这些肿瘤的自发转移。每只小鼠使用4、2和1 mg抗体的总剂量可减少黑色素瘤转移灶的数量和大小，并延长接受治疗动物的寿命。用4 mg单克隆抗体425.3的F(ab')2片段进行治疗不会影响M24met黑色素瘤的转移，这表明Fc部分对该抗体的抗转移作用有显著贡献。
