In situ activation of mouse alveolar macrophages by aerosolized liposomal IFN-gamma and muramyl tripeptide

Goldbach, Pierre; Dumont, Serge; Kessler, Rudolf W.; Poindron, Philippe; Stamm, A.

doi:10.1152/ajplung.1996.270.3.l429

Cited by 10 publications

(9 citation statements)

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“…Several studies demonstrated that IFN-γ synergizes with MTP-PE to increase tumoricidal activity and to induce secretion of cytokines [20,23,[28][29][30][31]. We found that MTP-PE synergizes with IFN-γ in inducing tumor killing by human macrophages, and augmenting secretion of TNF-α and IL-1β ( Fig.…”

Section: Preclinical Studies and Animal Trialsmentioning

confidence: 54%

Liposomal Muramyl Tripeptide Phosphatidylethanolamine: Targeting and Activating Macrophages for Adjuvant Treatment of Osteosarcoma

Nardin¹,

Lefebvre²,

Labroquère³

et al. 2006

CCDT

114

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About one third of osteosarcoma patients develop lung metastasis refractory to chemotherapy. Recent studies indicate that biological response modifiers activating the patient's immune system may help controlling minimal residual disease via pathways distinct from those used by cytotoxic drugs, and therefore prove effective against tumor resistance. Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthetic lipophilic glycopeptide capable of activating monocytes and macrophages to a tumoricidal state. When intercalated in multilamellar liposomes (L-MTP-PE) and injected intravenously, it targets lung, liver, and spleen macrophages. Therapeutic activity of L-MTP-PE was demonstrated in several preclinical models of experimental lung metastasis and in clinical trials in dogs with osteosarcoma. Although macrophage activation was shown to be directly involved in the in vivo anti-metastatic activity of this molecule, cytokine and chemokine secretion by activated macrophages could induce recruitment and stimulation of other immune cells, which may in turn indirectly contribute to the anti-tumor effect. L-MTP-PE has undergone clinical development in humans. In early trials, most side effects of L-MTP-PE were minimal. L-MTP-PE showed signs of efficacy in treatment of patients with recurrent osteosarcoma and the encouraging results from phase II studies led to a phase III trial conducted by the Children's Oncology Group in patients with newly diagnosed high-grade osteosarcoma. Patients were treated with or without L-MTP-PE in combination with multi-drug chemotherapy in adjuvant setting; significantly higher overall survival and disease-free survival were observed in the group receiving L-MTP-PE.

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Section: Preclinical Studies and Animal Trialsmentioning

confidence: 54%

Liposomal Muramyl Tripeptide Phosphatidylethanolamine: Targeting and Activating Macrophages for Adjuvant Treatment of Osteosarcoma

Nardin¹,

Lefebvre²,

Labroquère³

et al. 2006

CCDT

114

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“…If the infection were localized, it might be possible to use B30-MDP or another lipophilic derivative to localize the area of macrophage activation. Localization also increases potency of muramyl peptides as macrophage activators [49,125]. By localizing the macrophage activation, the danger of shock would be reduced.…”

Section: Limitations Of Macrophage Activationmentioning

confidence: 99%

Effects of Muramyl Peptides on Macrophages, Monokines, and Sleep

Pabst

Beranová-Giorgianni

Krueger

1999

Neuroimmunomodulation

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Muramyl peptides are fragments of peptidoglycan from the cell walls of bacteria. Because of their unique chemistry, the immune system recognizes that muramyl peptides are products of bacteria, and it responds by becoming activated to resist infection. This resistance to infection is nonspecific, and extends to unrelated species of bacteria, fungi, and viruses. A key mechanism of the resistance to infection is activation of macrophages. Macrophage activation results in increased production of microbicidal oxygen radicals like superoxide and peroxide, and in increased secretion of inflammatory cytokines like interleukin-1β and tumor necrosis factor-α. These cytokines, besides activating neutrophils, B lymphocytes, and T lymphocytes, act on the central nervous system to induce physiological responses like fever and sleep. These physiological responses also aid in combating infection. Muramyl peptides also activate macrophages and other cells of the immune system to kill cancer cells. Muramyl peptides and similar agents will become more important as therapeutic agents in the future, due to increasing resistance of microbes to antibiotics, and increasing numbers of patients with immunodeficiencies.

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“…MTP-PE, similarly to MDP, activates monocytes/macrophages, inducing activation of their cytotoxic function [10][11][12][13][14][15][16] and secretion of numerous cytokines, including TNF, IL-1, IL-6, IL-8, chemokine C-C motif ligand 2 (CCL2), prostaglandin E2 (PGE 2 ) and INF [9,[17][18][19][20][21][22][23]. Furthermore, L-MTP-PE induces the expression of adhesion molecules, including lymphocyte function-associated antigen (LFA)-1, intracellular adhesion molecule (ICAM)-1, and human leukocyte antigen (HLA)-DR which could be important for interaction with tumor cells [9,24].…”

Section: L-mtp-pe: a Synthetic Immune Modulator In A Liposome Drug Camentioning

confidence: 99%

Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases

Mori¹,

Ando²,

Heymann³

2008

Expert Review of Anticancer Therapy

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Osteosarcoma is the most common form of primary malignant bone tumor. The use of chemotherapy drugs with many side effects, including high-dose methotrexate, doxorubicin, cisplatin and ifosfamide, has greatly improved osteosarcoma survival compared with surgery alone. However, for 20 years, overall survival remained at a plateau of 60-70% in nonmetastatic disease and 20-30% in metastatic osteosarcoma owing to lung metastases. Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) is a new agent that improves overall osteosarcoma survival (chemotherapy without L-MTP-PE 70% versus with L-MTP-PE 78%; p = 0.03). L-MTP-PE offers additional benefit for osteosarcoma treatment in combination with chemotherapy, particularly ifosfamide-containing regimens. Clinical experience indicates that side effects such as fever are temporary and controlled or prevented with ibuprofen and/or acetoaminophen premedication; severe side effects are rare. Although surgery will remain the main approach for osteosarcoma treatment of lung metastases, L-MTP-PE combined with other modalities, including chemotherapy, appears to be of benefit in these patients as well.

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In situ activation of mouse alveolar macrophages by aerosolized liposomal IFN-gamma and muramyl tripeptide

Cited by 10 publications

References 0 publications

Liposomal Muramyl Tripeptide Phosphatidylethanolamine: Targeting and Activating Macrophages for Adjuvant Treatment of Osteosarcoma

Liposomal Muramyl Tripeptide Phosphatidylethanolamine: Targeting and Activating Macrophages for Adjuvant Treatment of Osteosarcoma

Effects of Muramyl Peptides on Macrophages, Monokines, and Sleep

Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases

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