白细胞介素-4受体导向细胞毒素疗法治疗异种移植模型中与艾滋病相关的卡波西肉瘤肿瘤
Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft model.
作者信息
Husain S R, Kreitman R J, Pastan I, Puri R K
机构信息
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland 20892, USA.
出版信息
Nat Med. 1999 Jul;5(7):817-22. doi: 10.1038/10541.
The elusive and enigmatic origin of AIDS-associated Kaposi's sarcoma (AIDS-KS) makes it a complex tumor and therefore difficult to treat. Here we demonstrate that AIDS-KS cells express surface interleukin-4 (IL-4) receptors, and that IL-4 toxin (IL-4(38-37)-PE38KDEL) is specifically cytotoxic to these cells. Intratumoral, intraperitoneal and intravenous administration of IL-4 toxin in nude mice with established subcutaneous AIDS-KS tumors caused considerable anti-tumor activity in a dose-dependent manner, with highest dose producing durable complete responses. Metabolic changes, including cachexia and lymphopenia, induced by KS tumors were prevented by IL-4 toxin treatment. This report establishes IL-4(38-37)-PE38KDEL as an experimental therapeutic agent for the treatment of AIDS-KS.
与艾滋病相关的卡波西肉瘤（AIDS-KS）难以捉摸且神秘的起源使其成为一种复杂的肿瘤，因此难以治疗。在此我们证明，AIDS-KS细胞表达表面白细胞介素-4（IL-4）受体，并且IL-4毒素（IL-4(38-37)-PE38KDEL）对这些细胞具有特异性细胞毒性。在已建立皮下AIDS-KS肿瘤的裸鼠中进行瘤内、腹腔内和静脉内注射IL-4毒素，以剂量依赖方式引起了相当大的抗肿瘤活性，最高剂量产生了持久的完全缓解。IL-4毒素治疗可预防由KS肿瘤诱导的包括恶病质和淋巴细胞减少在内的代谢变化。本报告确立了IL-4(38-37)-PE38KDEL作为治疗AIDS-KS的一种实验性治疗药物。
Zotero 插件