Abstract
The primary function of macrophages is to discriminate between 'self' and 'altered self' and to recognize and dispose of effete cells, cellular debris, and foreign invaders. Systemic activation of macrophages can be accomplished by intravenous administration of phospholipid liposomes containing natural or synthetic immunomodulators. Activated macrophages can eradicate cancer metastases in mice and spontaneous metastases in dogs with osteogenic sarcoma. Pharmaceutical-grade, freeze-dried phospholipid liposomes consisting of phosphatidylcholine and phosphatidylserine (7:3 molar ratio) and containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) have been studied in a multicenter Phase I trial and found to be safe. The optimal biological dose in humans was 0.5-2.0 mg/m2, whereas the maximal tolerated dose was 6.0 mg/m2. A Phase II trial using this commercial preparation of liposomes was recently completed in patients with recurrent osteosarcoma, who have a short disease-free interval following surgery. In patients receiving 24 weeks of liposome-MTP-PE therapy, time to relapse was significantly prolonged. In some patients who relapsed within 6 weeks of therapy completion, lung lesions were excised. The lesions were surrounded by a fibrous capsule with inflammatory macrophage infiltration. Neovascularization in the peripheral fibrosis was also noted. Collectively, the data demonstrate that therapy of drug-resistant tumor cells in humans can be accomplished by the systemic activation of macrophages with phospholipid liposomes containing the synthetic macrophage-activating agent lipophilic MTP-PE.
Original language | English (US) |
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Pages (from-to) | 325-340 |
Number of pages | 16 |
Journal | Advanced Drug Delivery Reviews |
Volume | 13 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1994 |
Keywords
- Clinical trials
- Liposomes
- Macrophages
- Metastasis
- Muramyl tripeptide
- Osteogenic sarcoma
ASJC Scopus subject areas
- Pharmaceutical Science