Pohl C, Renner C, Schwonzen M, Schobert I, Liebenberg V, Jung W, Wolf J, Pfreundschuh M, Diehl V
Klinik I für Innere Medizin, Universität zu Köln, Germany.
Int J Cancer. 1993 May 28;54(3):418-25. doi: 10.1002/ijc.2910540312.
The tumor-associated CD30 antigen is presently under study as a target for active specific immunotherapy of Hodgkin's lymphoma with anti-idiotypic antibodies. Internal image antibodies (Ab2 beta) 9G10 and 14G9 against the CD30-specific antibody HRS-4 (Ab1) have been described, which induce a CD30-specific T- and B-cell response in BALB/c mice and New Zealand white rabbits. In extension of this work, murine monoclonal anti-idiotypic Ab2 beta 9G10, mimicking structures of the nominal CD30 antigen, was used to generate monoclonal Ab3 in mice and polyclonal Ab3 in rabbits with specificity for CD30. The Ab2 beta 9G10-specific murine monoclonal Ab3 4A4 bound specifically to the 120-kDa band of CD30 present on Hodgkin cell lines and Hodgkin tumor tissue, and effectively inhibited binding of Ab1 HRS-4 to Ab2 9G10 as well as to CD30+ cells. Monoclonal Ab3 4A4 was cytotoxic for CD30+ cell lines in vitro and effectively prevented the s.c. growth of L540 cell tumors after passive i.v. administration in a SCID mouse tumor model. While this cytotoxic effect of the IgM subclass monoclonal Ab3 4A4 was due to complement activation, the murine monoclonal Ab1 HRS-4 and a polyclonal Ab3 preparation of IgG-subclass from New Zealand white rabbits were cytotoxic by an antibody-dependent cell-mediated mechanism in vitro. In conclusion, Ab2 beta 9G10 is able to induce a CD30-specific cytotoxic IgG and IgM response. Cytotoxicity was shown to be mediated by complement activation and antibody-dependent cell-mediated cytotoxicity in vitro and in vivo and across species barriers. Thus, the CD30-like Ab2 beta 9G10 may hold promise for effective active specific immunotherapy of human Hodgkin's lymphoma.
肿瘤相关的CD30抗原目前正作为霍奇金淋巴瘤主动特异性免疫治疗的靶点，采用抗独特型抗体进行研究。已报道了针对CD30特异性抗体HRS-4（Ab1）的内影像抗体（Ab2β）9G10和14G9，它们可在BALB/c小鼠和新西兰白兔中诱导CD30特异性T细胞和B细胞反应。在此工作的拓展中，模拟天然CD30抗原结构的鼠源单克隆抗独特型Ab2β 9G10被用于在小鼠中产生针对CD30具有特异性的单克隆Ab3，并在兔中产生多克隆Ab3。Ab2β 9G10特异性的鼠源单克隆Ab3 4A4可特异性结合霍奇金细胞系和霍奇金肿瘤组织上存在的120 kDa的CD30条带，并有效抑制Ab1 HRS-4与Ab2 9G10以及与CD30+细胞的结合。单克隆Ab3 4A4在体外对CD30+细胞系具有细胞毒性，并且在SCID小鼠肿瘤模型中经静脉被动给药后可有效阻止L540细胞瘤的皮下生长。虽然IgM亚类单克隆Ab3 4A4的这种细胞毒性作用是由于补体激活，但鼠源单克隆Ab1 HRS-4和来自新西兰白兔的IgG亚类多克隆Ab3制剂在体外通过抗体依赖的细胞介导机制具有细胞毒性。总之，Ab2β 9G1能够诱导CD30特异性的细胞毒性IgG和IgM反应。在体外和体内以及跨物种屏障中，细胞毒性显示是由补体激活和抗体依赖的细胞介导的细胞毒性介导的。因此，类似CD30的Ab2β 9G10可能有望用于人类霍奇金淋巴瘤的有效主动特异性免疫治疗。
