Ball E D, Keefe K A, Colby E
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756.
Cancer Res. 1987 Dec 15;47(24 Pt 1):6556-9.
We have previously described a panel of four monoclonal antibodies (MoAbs) reactive with antigens expressed on tumor cells from small cell carcinoma of the lung (SCCL). These IgM MoAbs are cytotoxic to SCCL cells in the presence of complement and thus have potential as reagents for the removal of SCCL cells contaminating bone marrow autografts. Therefore, we examined the cytotoxicity of these MoAbs against normal hematopoietic progenitor cells as a preliminary step toward their use in clinical trials. In this paper we report the results of treating normal bone marrow and peripheral blood mononuclear cells with the four IgM MoAbs, as well as an IgG2a MoAb that we have recently prepared against an SCCL cell line, DMS 406. Peripheral blood and bone marrow mononuclear cells were treated with the MoAbs alone or in combination, in the presence of rabbit complement, and then plated into colony-forming assays. Notably, only one MoAb, SCCL-1, had any demonstrable cytotoxicity against progenitor cells. This toxicity was limited to bone marrow burst-forming unit-erythroid and all classes of blood progenitor cells. A MoAb cocktail containing a combination of either four or five MoAbs + complement spared most marrow progenitor cells. These studies extend the base of information regarding the expression of SCCL-associated antigens on hematopoietic cells and indicate that selected MoAbs may be used safely for the removal of SCCL cells from autografts by complement-dependent lysis or other means.
我们之前描述过一组四种单克隆抗体(MoAbs),它们可与肺小细胞癌(SCCL)肿瘤细胞上表达的抗原发生反应。这些IgM单克隆抗体在补体存在的情况下对SCCL细胞具有细胞毒性,因此有潜力作为去除污染骨髓自体移植物的SCCL细胞的试剂。因此,作为将它们用于临床试验的初步步骤,我们检测了这些单克隆抗体对正常造血祖细胞的细胞毒性。在本文中,我们报告了用这四种IgM单克隆抗体以及我们最近针对SCCL细胞系DMS 406制备的一种IgG2a单克隆抗体处理正常骨髓和外周血单核细胞的结果。外周血和骨髓单核细胞在兔补体存在的情况下单独或联合用这些单克隆抗体处理,然后接种到集落形成试验中。值得注意的是,只有一种单克隆抗体SCCL-1对祖细胞有任何可证实的细胞毒性。这种毒性仅限于骨髓红系爆式集落形成单位和所有类型的血液祖细胞。含有四种或五种单克隆抗体加补体组合的单克隆抗体混合物可使大多数骨髓祖细胞免受影响。这些研究扩展了关于造血细胞上SCCL相关抗原表达的信息基础,并表明选定的单克隆抗体可通过补体依赖性溶解或其他方式安全地用于从自体移植物中去除SCCL细胞。