Strom T B, Kelley V R, Murphy J R, Nichols J, Woodworth T G
Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Annu Rev Med. 1993;44:343-53. doi: 10.1146/annurev.me.44.020193.002015.
With the exception of certain hematologic malignancies, the high affinity interleukin-2 (IL-2) receptor is only transiently expressed during the brief antigen-triggered proliferative burst of lymphocytes. Hence, we wondered whether administration of anti-IL-2 receptor (IL-2R) monoclonal antibody (mAb) or chimeric IL-2 toxins would provide a utilitarian way to achieve immunosuppression aimed directly at activated lymphocytes, or whether this approach could be used to treat IL-2R+ leukemia/lymphoma. Studies in preclinical autoimmune and transplant models indicate that this approach can be effective. The results of open, uncontrolled studies provide preliminary evidence that a chimeric IL-2 toxin is well tolerated at doses that may induce improvement in patients with IL-2R+ leukemia/lymphoma, as well as in patients with refractory rheumatoid arthritis or new-onset diabetes mellitus.
除某些血液系统恶性肿瘤外，高亲和力白细胞介素-2（IL-2）受体仅在淋巴细胞短暂的抗原触发增殖爆发期间短暂表达。因此，我们想知道给予抗IL-2受体（IL-2R）单克隆抗体（mAb）或嵌合IL-2毒素是否会提供一种实用的方法来实现直接针对活化淋巴细胞的免疫抑制，或者这种方法是否可用于治疗IL-2R +白血病/淋巴瘤。临床前自身免疫和移植模型的研究表明这种方法可能有效。开放、非对照研究的结果提供了初步证据，表明一种嵌合IL-2毒素在可能使IL-2R +白血病/淋巴瘤患者以及难治性类风湿性关节炎或新发糖尿病患者病情改善的剂量下具有良好的耐受性。
