Liao S K, Meranda C, Avner B P, Romano T, Husseini S, Kimbro B, Oldham R K
Biotherapeutics, Inc., Franklin, TN 37064.
Cancer Immunol Immunother. 1989;28(2):77-86. doi: 10.1007/BF00199106.
A panel of 14 monoclonal antibodies (MoAbs) (4 raised against breast cancer, 6 against colon cancer and 4 against melanoma) were used to phenotype frozen sections of tumor biopsies obtained from 110 patients, by avidin-biotin-peroxidase complex techniques. We observed heterogeneity of antigen expression among the multiple metastatic lesions of single patients, as well as among tumor lesions from different patients with similar tumor histotypes. A wide range of cross-reactivity of anti-(breast-carcinoma) and anti-(colon-carcinoma) MoAbs with other carcinoma histotypes and limited reactivity with melanoma and sarcoma was detected. Some of our anti-melanoma MoAbs were also found to cross-react with selected carcinomas. Nine of the 14 MoAbs most reactive with carcinomas of diverse histotypes have been identified. A mixture or 'cocktail' of different MoAbs could be selected for each individual patient in order to achieve binding of MoAbs with most, if not 100% of tumor cells. This study illustrates the approach that we have taken to individualize the cocktail of MoAbs for the development of patient-specific therapeutic immunoconjugates.
采用抗生物素蛋白-生物素-过氧化物酶复合物技术,用一组14种单克隆抗体(MoAbs)(4种针对乳腺癌,6种针对结肠癌,4种针对黑色素瘤)对110例患者的肿瘤活检冷冻切片进行表型分析。我们观察到单例患者的多个转移病灶之间以及不同患者具有相似肿瘤组织类型的肿瘤病灶之间抗原表达存在异质性。检测到抗(乳腺癌)和抗(结肠癌)MoAbs与其他癌组织类型有广泛的交叉反应,而与黑色素瘤和肉瘤的反应有限。我们还发现一些抗黑色素瘤MoAbs与某些特定的癌组织有交叉反应。已鉴定出14种与不同组织类型癌反应最强的MoAbs中的9种。可为每位患者选择不同MoAbs的混合物或“鸡尾酒”,以使MoAbs与大部分(即便不是100%)肿瘤细胞结合。本研究阐述了我们为开发患者特异性治疗性免疫缀合物而对MoAbs“鸡尾酒”进行个体化的方法。