LIPOSOME-ENCAPSULATED MTP-PE - A NOVEL BIOLOGIC AGENT FOR CANCER-THERAPY

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-M TP-PE), a new biologic response modifier, was designed to target the i mmunomodulator to monocytes and macrophages. Human monocytes/macrophag es phagocytize L-MTP-PE, with subsequent upregulation of interleukin ( IL)-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, a nd monocyte chemotactic and activating factor genes and with the produ ction and secretion of these cytokines in vitro. L-MTP-PE-activated ma crophages kill tumor but not normal cells in vitro. Following i.v. inf usion of L-MTP-PE into cancer patients, its uptake was demonstrated in liver, spleen, lung, and in and around metastases to lung. We also in vestigated whether L-MTP-PE therapy administered in a neoadjuvant sett ing could improve the disease-free interval in relapsed osteosarcoma p atients with lung metastasis. Patients received either a 12- or 24-wee k course of L-MTP-PE after surgical removal of all metastases. Followi ng L-MTP-PE infusion, induction of circulating TNF-alpha, IL-6, neopte rin, and C-reactive protein was demonstrated. Disease-free intervals w ere calculated from the day of surgery to the day of relapse in each g roup 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 in dicate that L-MTP-PE is an active agent against osteosarcoma and warra nts further investigation in an adjuvant setting.