Kawakami Koji, Kawakami Mariko, Husain Syed R, Puri Raj K
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Cancer Res. 2002 Jul 1;62(13):3575-80.
We demonstrate that pancreatic cancer tissues express receptors for interleukin (IL)-4 in situ at high density. Using the approach of selective receptor targeting, we have tested the efficacy of a recombinant cytotoxin IL4-Pseudomonas exotoxin A, which is composed of a targeting moiety (IL-4) and a mutated form of Pseudomonas exotoxin. Our results demonstrate that this molecule exerts vigorous antitumor activity against human pancreatic tumors implanted s.c. in immunodeficient animals. Sixty percent of animals treated with intratumoral injections of IL4-Pseudomonas exotoxin A experienced complete disappearance of established tumors. Animals with pancreatic tumors implanted orthotopically exhibited prolonged survival that was significantly greater by comparison with untreated animals. Thus, IL-4 receptor-targeted cytotoxin represents a potent agent that may provide an effective therapy for pancreatic cancer.
我们证明，胰腺癌组织原位高密度表达白细胞介素（IL）-4受体。采用选择性受体靶向方法，我们测试了重组细胞毒素IL4-绿脓杆菌外毒素A的疗效，该毒素由靶向部分（IL-4）和绿脓杆菌外毒素的突变形式组成。我们的结果表明，该分子对免疫缺陷动物皮下植入的人胰腺肿瘤具有强大的抗肿瘤活性。瘤内注射IL4-绿脓杆菌外毒素A治疗的动物中有60%已形成的肿瘤完全消失。原位植入胰腺肿瘤的动物生存期延长，与未治疗的动物相比有显著差异。因此，靶向IL-4受体的细胞毒素是一种有效的药物，可为胰腺癌提供有效的治疗。
