Dillman R O
Hoag Cancer Center, Newport Beach, California.
Ann Intern Med. 1989 Oct 1;111(7):592-603. doi: 10.7326/0003-4819-111-7-592.
To assess the current status of in-vivo use of monoclonal antibodies for treating cancer.
Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles.
More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis.
The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. RESULTS OF DATA SYNTHESES: Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents.
As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment.
评估单克隆抗体在癌症治疗中体内应用的现状。
通过使用MEDLINE和CANCERLIT进行计算机检索、查阅近期发表期刊的目录以及搜索已识别书籍和文章的参考文献，确定了1980年至1988年间发表的文献。
识别并选择了700多篇文章进行分析，包括同行评审文章和书籍章节。
对文献进行了综述，选择了235篇文章，这些文章与癌症治疗体内单克隆抗体的当前问题和未来应用以及与临床试验相关的毒性和疗效相关且具有代表性。
方法包括单独使用抗体（与补体或效应细胞相互作用或直接与某些细胞受体结合）和免疫缀合物（抗体与放射性同位素、药物、毒素或其他生物制剂偶联）。大多数经验来自鼠源抗体。单独使用抗体和放射性标记抗体的试验已证实了这种方法的可行性以及抗体在体内向肿瘤细胞的转运。然而，肿瘤细胞的异质性、细胞毒性的缺乏以及人抗鼠抗体的产生限制了临床疗效。尽管免疫缀合物非常有前景，但异质性和抗鼠免疫反应阻碍了这种方法，将抗体与细胞毒性剂进行化学或基因偶联的额外挑战也是如此。
作为一种治疗方式，单克隆抗体仍然很有前景，但它们的广泛应用将推迟数年。使用人源抗体并减少人抗球蛋白反应的新方法应有助于治疗。
