Article

Liposomal muramyl tripeptide phosphatidylethanolamine: Targeting and activating macrophages for adjuvant treatment of osteosarcoma.

IDM, Immuno-Designed Molecules, 172 rue de Charonne, 75011 Paris, France.
Current Cancer Drug Targets (Impact Factor: 3.58). 04/2006; 6(2):123-33. DOI: 10.2174/156800906776056473
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
164 Views
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteosarcoma (OS) is the most common non-hematologic malignant tumor of bone in adults and children. As sarcomas are more common in adolescents and young adults than most other forms of cancer, there are a significant num-ber of years of life lost secondary to these malignancies. OS is associated with a poor prognosis secondary to a high grade at presentation, resistance to chemotherapy and a propensity to metastasize to the lungs. Current OS management involves both chemotherapy and surgery. The incorporation of cytotoxic chemotherapy into therapeutic regimens escalated cure rates from <20% to current levels of 65-75%. Furthermore, limb-salvage surgery is now offered to the majority of OS pa-tients. Despite advances in chemotherapy and surgical techniques over the past three decades, there has been stagnation in patient survival outcome improvement, especially in patients with metastatic OS. Thus, there is a critical need to identify novel and directed therapy for OS. Several Phase I trials for sarcoma therapies currently ongoing or recently completed have shown objective responses in OS. Novel drug delivery mechanisms are currently under phase II and III clinical trials. Furthermore, there is an abundance of preclinical research which holds great promise in the development of future OS-directed therapeutics. Our continuously improving knowledge of the molecular and cell-signaling pathways involved in OS will translate into more effective therapies for OS and ultimately improved patient survival. The present review will provide an overview of current therapies, ongoing clinical trials and therapeutic targets under investigation for OS.
    Current Cancer Therapy Reviews 02/2013; 9(1):55-77. DOI:10.2174/157339413805076369
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary bone tumors are rare, but their treatments have enjoyed considerable improvements in life expectancy because of chemotherapy. When combined with advances in surgery, patients can now expect lives and limbs to behave with greater longevity and normality. The challenge now is how to raise the plateau of survival, and that means finding a successful way to treat metastatic or unsalvageable local disease. It is clear that conventional chemotherapy has limitations and that the answer may lie in a better understanding of the intricate molecular workings of cancer and the pathways that lead to the latter’s growth, invasion, and dissemination. There have been great strides made in dissecting out the metastatic cascade with numerous important pathways and molecular switches identified. This has led to the introduction of a number of new drugs and molecules aimed at targeting the molecular vulnerabilities of cancer, allowing greater control of growth, invasion, and metastasis. Some of these have had a large impact on musculoskeletal malignancies. Future successes in treatment will require multimodal targeting of tumors whose signatures will be a composite of histologic and molecular markers that will pave the way for personalization of treatment strategies.
    06/2014; 2(6). DOI:10.1007/s40137-014-0055-0

Full-text (2 Sources)

Download
29 Downloads
Available from
May 23, 2014