Abstract
Liposome-encapsulated muramyl tripeptide phosphatidylethanol-amine (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)-1α;, IL-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, 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-α, 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.
Original language | English (US) |
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Pages (from-to) | 286-292 |
Number of pages | 7 |
Journal | Journal of Immunotherapy |
Volume | 14 |
Issue number | 4 |
DOIs | |
State | Published - Nov 1993 |
Keywords
- Cytokine
- Liposome encapsulated MTP-PE
- Lung metastasis
- Osteosarcoma
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology
- Cancer Research