Schlebusch H, Wagner U, Grünn U, Schultes B
Center for Gynecology and Obstetrics, University of Bonn, Germany.
Hybridoma. 1995 Apr;14(2):167-74. doi: 10.1089/hyb.1995.14.167.
A new concept of oncological immunotherapy comprises the attempt to trigger the immune system of the host into a response against tumor cells. Antiidiotypic antibodies bearing the internal image of an antigen expressed on the surface of the tumor seem to be most suited for this purpose. We have generated a murine antiidiotypic antibody (ACA 125) functionally imitating the tumor-associated antigen CA 125, which can be detected in about 80% of ovarian carcinomas. The hybridoma cell was adapted to serum-free medium and antibody was produced in a hollow fiber cell culture system (Technomouse). ACA 125 (Ab2) shows high affinity for the paratope of Ab1 (affinity constant: 2.3 x 10(9) liters/mol) and binding of Ab2 to Ab1 is completely inhibited by the nominal antigen. Application of F(ab')2 fragments of ACA 125 to rats lead to an anti-CA 125 immunity by production of IgG and IgM antiantiidiotypic antibodies (Ab3) that bind to both ACA 125 and CA 125. Furthermore the induction of a non-MHC-restricted cell-mediated cytotoxicity for human ovarian adenocarcinoma cell line NIH-OVCAR3 (expressing CA 125 on its surface) could be proved; additionally complement-dependent cytotoxicity (CDC) as well as an antibody-dependent cellular cytotoxicity (ADCC) was observed. Thus, monoclonal antiidiotypic antibody ACA 125 fulfills recent criteria for an antibody, which might be successful in immunotherapy using the anti-idiotypic network approach.
肿瘤免疫疗法的一个新概念包括试图激发宿主的免疫系统对肿瘤细胞产生反应。携带肿瘤表面表达抗原内部影像的抗独特型抗体似乎最适合此目的。我们已产生一种功能上模拟肿瘤相关抗原CA 125的鼠抗独特型抗体（ACA 125），约80%的卵巢癌中可检测到该抗原。杂交瘤细胞适应无血清培养基，并在中空纤维细胞培养系统（Technomouse）中产生抗体。ACA 125（Ab2）对Ab1的互补决定区显示出高亲和力（亲和常数：2.3×10⁹升/摩尔），且Ab2与Ab1的结合被标称抗原完全抑制。将ACA 125的F(ab')₂片段应用于大鼠，通过产生与ACA 125和CA 125都结合的IgG和IgM抗抗独特型抗体（Ab3），导致产生抗CA 125免疫。此外，可证明对人卵巢腺癌细胞系NIH-OVCAR3（其表面表达CA 125）诱导了非MHC限制的细胞介导细胞毒性；另外还观察到补体依赖性细胞毒性（CDC）以及抗体依赖性细胞毒性（ADCC）。因此，单克隆抗独特型抗体ACA 125符合近期关于一种抗体的标准，该抗体可能在使用抗独特型网络方法的免疫疗法中取得成功。
