Sears H F, Herlyn D, Herlyn M, Steplewski Z, Grotzinger P, Koprowski H
Cancer. 1982 Mar 15;49(6):1231-5. doi: 10.1002/1097-0142(19820315)49:6<1231::aid-cncr2820490626>3.0.co;2-a.
The binding of mouse hybridoma monoclonal antibodies directed against human colon carcinomas was studied using an ex vivo perfusion model of a freshly resected human colon segment containing a carcinoma. Tumor and the surrounding normal bowel is exposed to the putative tumor antigen through an intact vascular system without mechanical or enzymatic cellular alteration. An hour of perfusion was conducted on thirty specimens using five different monoclonal anticolorectal cancer (ACRC) antibodies. Three were gamma 1, one gamma 2A and one was IgM isotype. Control anti-influenza virus monoclonal antibodies were used to demonstrate absence of nonspecific binding. Our antibody 17-1A bound to the colon cancer in seven of ten trials, but bound to normal colon cells also in four of these trials. The IgM antibody did not bind to anything. The two gamma 1 antibodies that recognize an antigen shed from the surface of the cell did not demonstrate cell binding under conditions of this study, and conditions to detect this will have to be modified. The ex vivo perfusion model as performed in this study can provide a valuable adjunct to evaluate the potential clinical utility for antibody conjugate radiolocalization or therapy of colon cancer.
利用含有癌组织的新鲜切除的人结肠段的离体灌注模型，研究了针对人结肠癌的小鼠杂交瘤单克隆抗体的结合情况。肿瘤和周围正常肠段通过完整的血管系统暴露于假定的肿瘤抗原，而不会发生机械性或酶促性细胞改变。使用五种不同的抗结直肠癌（ACRC）单克隆抗体对30个标本进行了一小时的灌注。其中三种是γ1型，一种是γ2A型，一种是IgM型。使用对照抗流感病毒单克隆抗体来证明不存在非特异性结合。我们的抗体17-1A在十次试验中的七次与结肠癌结合，但在其中四次试验中也与正常结肠细胞结合。IgM抗体未与任何物质结合。在本研究条件下，识别从细胞表面脱落的抗原的两种γ1抗体未显示细胞结合，检测此情况的条件必须加以修改。本研究中所采用的离体灌注模型可为评估抗体偶联物放射性定位或结肠癌治疗的潜在临床效用提供有价值的辅助手段。
