Mabry M, Speak J A, Griffin J D, Stahel R A, Bernal S D
J Clin Invest. 1985 May;75(5):1690-5. doi: 10.1172/JCI111877.
SM-1 is a murine monoclonal antibody strongly reactive with a cell membrane antigen of small cell carcinoma (SCC) of the lung but unreactive with the membrane of most other carcinomas and normal tissues including normal bone marrow. We have found that in the presence of human complement, SM-1 antibody is highly cytotoxic to SCC cells. Using three treatments with antibody and complement, more than 99% of SCC cells in culture were lysed, as determined by the chromium release and clonogenic assays. Similar efficiency of SCC cell lysis was observed when one SM-1 antibody treatment was followed by three treatments with human complement. In contrast, there was little antibody-dependent lysis of non-small cell lung cancer cells, other carcinomas, and leukemia cell lines. The amount of chromium released from normal bone marrow cells treated with SM-1 antibody and complement was minimal and was mainly due to the effect of complement alone. Clonogenic assays, including colony-forming unit-granulocytic/monocytic, erythroid burst-forming unit, and colony-forming unit-granulocytic/erythroid/monocytic/megakaryocytic, also showed no significant SM-1 antibody-dependent cytotoxicity on normal bone marrow precursors. Since SM-1 antibody is selectively cytotoxic to SCC cells in the presence of human complement, it is a potentially useful agent for the selective eradication of tumor cell contamination in marrows of patients with metastatic small cell lung cancer and possibly for in vivo serotherapy.
SM-1是一种鼠单克隆抗体,与肺小细胞癌(SCC)的细胞膜抗原强烈反应,但与大多数其他癌组织及包括正常骨髓在内的正常组织的细胞膜无反应。我们发现,在人补体存在的情况下,SM-1抗体对SCC细胞具有高度细胞毒性。通过三次抗体与补体联合处理,采用铬释放试验和克隆形成试验测定,培养的SCC细胞中有超过99%被裂解。当先用一次SM-1抗体处理,随后进行三次人补体处理时,观察到了类似的SCC细胞裂解效率。相比之下,非小细胞肺癌细胞、其他癌组织和白血病细胞系几乎没有抗体依赖性裂解。用SM-1抗体和补体处理的正常骨髓细胞释放的铬量极少,主要是补体单独作用的结果。克隆形成试验,包括粒细胞/单核细胞集落形成单位、红系爆式集落形成单位以及粒细胞/红系/单核细胞/巨核细胞集落形成单位,也显示SM-1抗体对正常骨髓前体细胞无明显的抗体依赖性细胞毒性。由于SM-1抗体在人补体存在的情况下对SCC细胞具有选择性细胞毒性,它可能是用于选择性清除转移性小细胞肺癌患者骨髓中肿瘤细胞污染以及可能用于体内血清疗法的一种有用药物。