Comparative efficacy of liposomes containing synthetic bacterial cell wall analogues for tumoricidal activation of monocytes and macrophages

Utsugi, Teruhiro; Nii, Akihiko; Fan, Dominic; Pak, Charles C.; Denkins, Yvonne; Hoogevest, Peter van; Fidler, Isaiah J.

doi:10.1007/bf01756592

Cited by 19 publications

(3 citation statements)

References 41 publications

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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: 60%

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: 60%

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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“…"In situ" is regarded as liposomes that are formed before clinical use [90]. The commercial product of Mepacthas adopted this method for production.…”

Section: In Situ Preparation Of Liposomesmentioning

confidence: 99%

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives

Liu¹,

Chen²,

Zhang³

2022

Molecules

477

239

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Liposomes have been considered promising and versatile drug vesicles. Compared with traditional drug delivery systems, liposomes exhibit better properties, including site-targeting, sustained or controlled release, protection of drugs from degradation and clearance, superior therapeutic effects, and lower toxic side effects. Given these merits, several liposomal drug products have been successfully approved and used in clinics over the last couple of decades. In this review, the liposomal drug products approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are discussed. Based on the published approval package in the FDA and European public assessment report (EPAR) in EMA, the critical chemistry information and mature pharmaceutical technologies applied in the marketed liposomal products, including the lipid excipient, manufacturing methods, nanosizing technique, drug loading methods, as well as critical quality attributions (CQAs) of products, are introduced. Additionally, the current regulatory guidance and future perspectives related to liposomal products are summarized. This knowledge can be used for research and development of the liposomal drug candidates under various pipelines, including the laboratory bench, pilot plant, and commercial manufacturing.

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“…There is a long-standing interest in liposomal muramyl (tri) peptides for inducing immune activation (69,70). Recently, renewed interest in MDP sparked, as it was shown to induce a state of DC hyperactivity, when combined with TLR ligands (55,56).…”

Section: Discussionmentioning

confidence: 99%

Incorporation of Toll-Like Receptor Ligands and Inflammasome Stimuli in GM3 Liposomes to Induce Dendritic Cell Maturation and T Cell Responses

et al. 2022

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Cancer vaccination aims to activate immunity towards cancer cells and can be achieved by delivery of cancer antigens together with immune stimulatory adjuvants to antigen presenting cells (APC). APC maturation and antigen processing is a subsequent prerequisite for T cell priming and anti-tumor immunity. In order to specifically target APC, nanoparticles, such as liposomes, can be used for the delivery of antigen and adjuvant. We have previously shown that liposomal inclusion of the ganglioside GM3, an endogenous ligand for CD169, led to robust uptake by CD169-expressing APC and resulted in strong immune responses when supplemented with a soluble adjuvant. To minimize the adverse effects related to a soluble adjuvant, immune stimulatory molecules can be incorporated in liposomes to achieve targeted delivery of both antigen and adjuvant. In this study, we incorporated TLR4 (MPLA) or TLR7/8 (3M-052) ligands in combination with inflammasome stimuli, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) or muramyl dipeptide (MDP), into GM3 liposomes. Incorporation of TLR and inflammasome ligands did not interfere with the uptake of GM3 liposomes by CD169-expressing cells. GM3 liposomes containing a TLR ligand efficiently matured human and mouse dendritic cells in vitro and in vivo, while inclusion of PGPC or MDP had minor effects on maturation. Immunization with MPLA-containing GM3 liposomes containing an immunogenic synthetic long peptide stimulated CD4+ and CD8+ T cell responses, but additional incorporation of either PGPC or MDP did not translate into stronger immune responses. In conclusion, our study indicates that TLRL-containing GM3 liposomes are effective vectors to induce DC maturation and T cell priming and thus provide guidance for further selection of liposomal components to optimally stimulate anti-cancer immune responses.

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Comparative efficacy of liposomes containing synthetic bacterial cell wall analogues for tumoricidal activation of monocytes and macrophages

Cited by 19 publications

References 41 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

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives

Incorporation of Toll-Like Receptor Ligands and Inflammasome Stimuli in GM3 Liposomes to Induce Dendritic Cell Maturation and T Cell Responses

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