LIPOSOME-ENCAPSULATED MTP-PE - A NOVEL BIOLOGIC AGENT FOR CANCER-THERAPY
LIPOSOME-ENCAPSULATED MTP-PE - A NOVEL BIOLOGIC AGENT FOR CANCER-THERAPY
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DOI：
10.1097/00002371-199311000-00006
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发表时间：
1993-11-01
影响因子：
3.9
通讯作者：
KLEINERMAN, ES
中科院分区：
文献类型：
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作者：
ASANO, T;KLEINERMAN, ES
脂质体包封的muramyl三肽磷脂酰乙醇胺（L-MTP-PE）是一种新的生物反应调节剂，旨在将其靶向单核细胞和巨噬细胞。人单核/巨噬细胞吞噬L-MTP-PE，随后上调白细胞介素(IL)-1 α、IL-1 β、IL-6、IL-8、肿瘤坏死因子(TNF)- α和单核细胞趋化因子和激活因子基因，并在体外产生和分泌这些细胞因子。l - mtp - pe活化的巨噬细胞能杀伤肿瘤细胞，但不能杀伤正常细胞。在癌症患者静脉注射L-MTP-PE后，发现其在肝脏、脾脏、肺以及肺转移灶内和周围均有摄取。我们还研究了L-MTP-PE治疗在新辅助环境下是否可以改善肺转移的复发骨肉瘤患者的无病间期。在手术切除所有转移瘤后，患者接受12周或24周的L-MTP-PE治疗。L-MTP-PE输注后，循环tnf - α、IL-6、新蝶呤和c反应蛋白的诱导被证实。计算各组从手术当日至复发当日的无病时间间隔，并与历史对照组的无病时间间隔进行比较。接受24周L-MTP-PE治疗的患者复发时间明显延长（p < 0.03）。这些数据表明，L-MTP-PE是一种抗骨肉瘤的活性药物，值得进一步研究。
Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), a new biologic response modifier, was designed to target the immunomodulator to monocytes and macrophages. Human monocytes/macrophages phagocytize L-MTP-PE, with subsequent upregulation of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and monocyte chemotactic and activating factor genes and with the production and secretion of these cytokines in vitro. L-MTP-PE-activated macrophages kill tumor but not normal cells in vitro. Following i.v. infusion of L-MTP-PE into cancer patients, its uptake was demonstrated in liver, spleen, lung, and in and around metastases to lung. We also investigated whether L-MTP-PE therapy administered in a neoadjuvant setting could improve the disease-free interval in relapsed osteosarcoma patients with lung metastasis. Patients received either a 12- or 24-week course of L-MTP-PE after surgical removal of all metastases. Following L-MTP-PE infusion, induction of circulating TNF-alpha, IL-6, neopterin, and C-reactive protein was demonstrated. Disease-free intervals were calculated from the day of surgery to the day of relapse in each group and were compared with the disease-free interval for a historical control group. Those patients receiving 24 weeks of L-MTP-PE showed a significant (p < 0.03) prolongation in time to relapse. These data indicate that L-MTP-PE is an active agent against osteosarcoma and warrants further investigation in an adjuvant setting.