Frödin J E, Faxas M E, Hagström B, Lefvert A K, Masucci G, Nilsson B, Steinitz M, Unger P, Mellstedt H
Department of Oncology (Radiumhemmet) and Immunologic, Karolinska Hospital, Stockholm, Sweden.
Hybridoma. 1991 Aug;10(4):421-31. doi: 10.1089/hyb.1991.10.421.
Forty-three patients with metastatic colorectal carcinoma (CRC) were treated with the unconjugated mouse monoclonal antibody (MAb) 17-1A (ab1) only. The presence of antiidiotypic antibodies (ab2) and anti-antiidiotypic antibodies (ab3) were analyzed using an ELISA technique and a mixed hemadsorption assay respectively. Ninety-five percent (41/43) of the patients developed ab2 both of the IgM and the IgG classes. Forty-seven percent (20/43) of the patients had detectable ab3 after therapy, two of them also before administration of MAb 17-1A. Binding in vitro of ab3 (ab1) to CRC cells could be specifically inhibited by ab1. Ab3 bound to human monoclonal antiidiotypic antibodies and to a goat antiidiotypic antibody (ab2). Both these ab2 were directed against MAb 17-1A (ab1). There was a strong correlation between the presence of ab3 and the clinical outcome. Ab3+ patients survived significantly longer than those who did not develop ab3 antibodies, 80 weeks vs 38 weeks (p less than 0.001). A statistically significant correlation was found between the presence of ab3 and the anti-tumor response (CR + PR + MR + SD) (p = 0.01). Thus, induction of an antiidiotypic cascade seems to be an important antitumor effector function of MAb in the treatment of cancer patients.
43例转移性结直肠癌（CRC）患者仅接受了非结合型小鼠单克隆抗体（MAb）17-1A（ab1）治疗。分别采用酶联免疫吸附测定（ELISA）技术和混合血细胞吸附试验分析抗独特型抗体（ab2）和抗抗独特型抗体（ab3）的存在情况。95%（41/43）的患者产生了IgM和IgG类的ab2。47%（20/43）的患者在治疗后可检测到ab3，其中2例在给予MAb 17-1A之前也可检测到。ab3（ab1）与CRC细胞的体外结合可被ab1特异性抑制。ab3与人单克隆抗独特型抗体和山羊抗独特型抗体（ab2）结合。这两种ab2均针对MAb 17-1A（ab1）。ab3的存在与临床结果之间存在强烈相关性。产生ab3的患者存活时间明显长于未产生ab3抗体的患者，分别为80周和38周（p<0.001）。ab3的存在与抗肿瘤反应（CR+PR+MR+SD）之间存在统计学上的显著相关性（p=0.01）。因此，诱导抗独特型级联反应似乎是MAb在癌症患者治疗中的一种重要抗肿瘤效应功能。
