Sweeney E B, Murphy J R
Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA.
Essays Biochem. 1995;30:119-31.
The results from the phase I/II studies of the intravenous administration of DAB486-IL-2 to patients with refractory haematological malignancies have now proven in principle the feasibility of fusion toxin therapy in man. Indeed, the cell-surface receptor-specific intoxication of neoplastic cells through the catalytic ADP-ribosylation of EF-2 is the prototype of a new class of biological response modifiers that may be generally applicable. In those circumstances where either the de novo expression or up-regulation of a cell-surface receptor can be associated with human disease [e.g. the up-regulation of the epidermal growth factor (EGF) receptor on breast cancer], it should be possible to construct genetically a DT-related/growth factor fusion protein to produce an experimental biological treatment of that malignancy. The EGF receptor-targeted fusion toxin DAB389-EGF has within the last year begun human phase I clinical trials. The pre-clinical development of DAB389-IL-7 has begun with the anticipation that this novel fusion toxin will be evaluated in the treatment of the acute leukaemias in which the IL-7R has been shown to be present.
对难治性血液系统恶性肿瘤患者静脉注射DAB486-IL-2的I/II期研究结果已原则上证明了融合毒素疗法在人体中的可行性。实际上，通过EF-2的催化性ADP-核糖基化使肿瘤细胞发生细胞表面受体特异性中毒，是一类可能普遍适用的新型生物反应调节剂的原型。在那些细胞表面受体的从头表达或上调可能与人类疾病相关的情况下[例如乳腺癌上表皮生长因子（EGF）受体的上调]，应该有可能通过基因构建一种与DT相关的/生长因子融合蛋白，以产生针对该恶性肿瘤的实验性生物治疗方法。靶向EGF受体的融合毒素DAB389-EGF已于去年开始进行人体I期临床试验。DAB389-IL-7的临床前研发已经启动，预期这种新型融合毒素将用于治疗已证明存在IL-7R的急性白血病。
