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SM-1单克隆抗体与人补体在选择性杀伤肺小细胞癌中的应用。

Use of SM-1 monoclonal antibody and human complement in selective killing of small cell carcinoma of the lung.

作者信息

Mabry M, Speak J A, Griffin J D, Stahel R A, Bernal S D

出版信息

J Clin Invest. 1985 May;75(5):1690-5. doi: 10.1172/JCI111877.

DOI:10.1172/JCI111877
PMID:2987309
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC425512/
Abstract

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.

摘要

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。

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Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin).人类癌症会不同程度地表达补体抑制蛋白CD46(膜辅因子蛋白)、CD55(衰变加速因子)和CD59(保护素)。
Am J Pathol. 1996 Jul;149(1):129-42.
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Effective removal of SCLC cells from human bone marrow. Use of four monoclonal antibodies and immunomagnetic beads.从小鼠骨髓中有效去除小细胞肺癌细胞。使用四种单克隆抗体和免疫磁珠。
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本文引用的文献

1
High-dose combination chemotherapy with autologous bone marrow transplantation in adult solid tumors.成人实体瘤的大剂量联合化疗与自体骨髓移植
Cancer. 1980 Jun 15;45(12):3075-85. doi: 10.1002/1097-0142(19800615)45:12<3075::aid-cncr2820451233>3.0.co;2-8.
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Elimination of leukemic cells from human bone marrow using monoclonal antibody and complement.使用单克隆抗体和补体从人骨髓中清除白血病细胞。
Cancer Res. 1983 Mar;43(3):1389-94.
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Intensive chemoradiotherapy with autologous marrow transplantation for small cell carcinoma of the lung.
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Membrane antigen in small cell carcinoma of the lung defined by monoclonal antibody SM1.由单克隆抗体SM1界定的肺小细胞癌中的膜抗原。
Cancer Res. 1984 Jan;44(1):265-70.
6
Autologous bone marrow transplantation in the therapy of small cell carcinoma of the lung.自体骨髓移植在肺癌小细胞癌治疗中的应用
Cancer Res. 1982 Oct;42(10):4270-5.
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High-dose cyclophosphamide with autologous marrow transplantation as initial treatment of small cell carcinoma of the bronchus.高剂量环磷酰胺联合自体骨髓移植作为支气管小细胞癌的初始治疗方法。
Cancer Chemother Pharmacol. 1982;8(1):31-4. doi: 10.1007/BF00292868.
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Long-term survival in small cell carcinoma of the lung.小细胞肺癌的长期生存
JAMA. 1980 Jul 18;244(3):247-50.
9
Autologous bone marrow transplantation following high-dose chemotherapy with cyclophosphamide, BCNU and VP-16 in small cell carcinoma of the lung and a review of current literature.环磷酰胺、卡莫司汀和顺铂足叶乙苷大剂量化疗后自体骨髓移植治疗小细胞肺癌及当前文献综述
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10
Complement inhibitor(s) released by leukocytes. III. Evidence for a "new" C1 inhibitor in the supernatants of short-term cultures of mouse spleen and thymus cells.白细胞释放的补体抑制剂。III. 小鼠脾脏和胸腺细胞短期培养上清液中“新型”C1抑制剂的证据。
J Immunol. 1975 Oct;115(4):1091-4.