Winkler U, Gottstein C, Schön G, Kapp U, Wolf J, Hansmann M L, Bohlen H, Thorpe P, Diehl V, Engert A
Medizinische Universitätsklinik I, Köln, Germany.
Blood. 1994 Jan 15;83(2):466-75.
To evaluate the effects of deglycosylated ricin A-chain (dgA) immunotoxins against disseminated Hodgkin's lymphoma, we used RFT5.dgA (CD25) and IRac.dgA (70 kD) to treat L540Cy Hodgkin cells in severely immunodeficient SCID mice. In this model, more than 90% of the animals developed multiple lymphomas in various organs such as the lymph nodes, liver, bone marrow, and extranodal sites that killed untreated animals after a mean survival time (MST) of 36.3 days. A single intraperitoneal injection of 8 micrograms of either immunotoxin rendered 95% (RFT5.dgA) and 93% (IRac.dgA), respectively, of mice tumor-free when applied 1 day after tumor challenge. The MST of the RFT5.dgA-treated group was extended by more than 80 days (P < .00001). SCID mice treated 12 days after tumor challenge had lower remission rates (46%), suggesting that the antitumor effect of the immunotoxins depends on the number of tumor cells present. We conclude that ricin A-chain immunotoxins have potent antitumor effects against disseminated Hodgkin's tumors in SCID mice and that this model is ideally suited for the evaluation of different immunotoxin treatment modalities.
为了评估去糖基化蓖麻毒素A链（dgA）免疫毒素对播散性霍奇金淋巴瘤的作用，我们使用RFT5.dgA（CD25）和IRac.dgA（70 kD）对严重免疫缺陷的SCID小鼠体内的L540Cy霍奇金细胞进行治疗。在该模型中，超过90%的动物在淋巴结、肝脏、骨髓和结外部位等多个器官中发生多发性淋巴瘤，导致未经治疗的动物在平均生存时间（MST）为36.3天后死亡。在肿瘤接种后1天腹腔注射8微克任何一种免疫毒素，分别使95%（RFT5.dgA）和93%（IRac.dgA）的小鼠无肿瘤。RFT5.dgA治疗组的平均生存时间延长了80多天（P <.00001）。在肿瘤接种后12天进行治疗的SCID小鼠缓解率较低（46%），这表明免疫毒素的抗肿瘤作用取决于现存肿瘤细胞的数量。我们得出结论，蓖麻毒素A链免疫毒素对SCID小鼠体内的播散性霍奇金肿瘤具有强大的抗肿瘤作用，并且该模型非常适合评估不同的免疫毒素治疗方式。
