TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data

Gamie, Zakareya; Kapriniotis, Konstantinos; Papanikolaou, Dimitra; Haagensen, Emma J.; Ribeiro, Ricardo; Dalgarno, Kenneth; Krippner‐Heidenreich, Anja; Gerrand, Craig; Tsiridis, Eleftherios; Rankin, Kenneth

doi:10.1016/j.canlet.2017.08.036

Cited by 33 publications

(18 citation statements)

References 142 publications

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“…However, the implementation of novel therapies could help to improve the survival of patients suffering from sarcoma in the future. In this line, TRAIL has been tested in distinct types of sarcoma both in pre-clinical studies and clinical trials [ 5 ]. However, the potential of TRAIL as possible treatment in sarcomas has been explored in all cases using the soluble form of TRAIL [ 28 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, there is an urgent need to develop and test novel therapeutic strategies in order to improve prognosis of sarcoma patients [ 4 ]. Among the novel anti-tumor agents used, apoptosis ligand 2/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has been tested both in pre-clinical studies and clinical trials in some types of sarcoma [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, TRAIL-based therapeutic strategies were developed and used in several phase I/II clinical trials on a wide variety of human cancers [ 8 , 9 , 10 ]. However, although TRAIL-based therapies were proven safe, about 50% of human cancers were intrinsically resistant to TRAIL since the clinical studies using TRAIL showed limited therapeutic activity of this death ligand in different types of cancer [ 9 , 11 , 12 ] including sarcoma [ 5 ]. Therefore, novel formulations of TRAIL with improved bioactivity and combination of TRAIL with sensitizing agents could be plausible strategies to overcome TRAIL resistance [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticles Decorated with TNF-Related Aptosis-Inducing Ligand (TRAIL) Are More Cytotoxic than Soluble Recombinant TRAIL in Sarcoma

Gallego-Lleyda

Miguel

Anel

et al. 2018

IJMS

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Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome for some types of sarcomas. However, novel therapeutic strategies to treat sarcomas are necessary. TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand initially described as capable of inducing apoptosis on tumor cell while sparing normal cells. Only few clinical trials have used TRAIL-based treatments in sarcoma, but they show only low or moderate efficacy of TRAIL. Consequently, novel TRAIL formulations with an improved TRAIL bioactivity are necessary. Our group has developed a novel TRAIL formulation based on tethering this death ligand on a lipid nanoparticle surface (LUV-TRAIL) resembling the physiological secretion of TRAIL as a trasmembrane protein inserted into the membrane of exosomes. We have already demonstrated that LUV-TRAIL shows an improved cytotoxic activity when compared to soluble recombinant TRAIL both in hematological malignancies and epithelial-derived cancers. In the present study, we have tested LUV-TRAIL in several human sarcoma tumor cell lines with different sensitivity to soluble recombinant TRAIL, finding that LUV-TRAIL was more efficient than soluble recombinant TRAIL. Moreover, combined treatment of LUV-TRAIL with distinct drugs proved to be especially effective, sensitizing even more resistant cell lines to TRAIL.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticles Decorated with TNF-Related Aptosis-Inducing Ligand (TRAIL) Are More Cytotoxic than Soluble Recombinant TRAIL in Sarcoma

Gallego-Lleyda

Miguel

Anel

et al. 2018

IJMS

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“…TRAIL (TNF-related apoptosis-inducing ligand) is an anticancer gene. Its protein product can speci cally kill cancer cells without harming normal cells [9][10][11][12][13]. Owing to its tumor cell-speci c killing effect, TRAIL has been widely used in preclinical and clinical studies [12,[14][15][16][17][18][19][20][21][22][23]].…”

Section: Discussionmentioning

confidence: 99%

Intracranial Delivery of Synthetic mRNA Using Common Transfection Reagent

Peng¹,

Guo²,

He³

et al. 2020

Preprint

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Abstract Background: Owing to messenger RNA’s unique biological advantages, it has received increasing attention to be used as a therapeutic gene carrier, known as mRNA-based gene therapy. It is critical to precisely deliver specific mRNA into targeted part of the body to achieve effective treatment.Methods: In the present study, a mouse model of intracranial delivery of synthetic mRNA was established using commonly used transfection reagent. Synthetic luciferase mRNAs were wrapped with two different transfection reagents and microinjected into the brain at the fixed point. The expression status of delivered mRNA was monitored by a small animal imaging system. The possible reagent-induced biological toxicity was evaluated by behavioral and blood biochemical measurements. Synthetic modified TRAIL mRNA was also used as an example of therapeutic application.Results: This model demonstrated that synthetic mRNA could be successfully delivered into the brain with commonly used transfection reagents without measurable toxicity. The expression of exogenous mRNA persisted in a reasonable period following intracranial injection.Conclusions: This mouse model of intracranial delivery of synthetic mRNA can be applied in preclinical studies of mRNA-based gene therapy.

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“…TNF-related apoptosis-inducing ligand (TRAIL) delivered by AD-MSCs have an anti-tumorigenic effect on osteosarcoma. AD-MSC-delivered TRAIL efficiently kills OS cells, since MSCs confer a longer half-life with stable TRAIL delivery and the secretion of synergizing factors [95,96]. A clinical trial (NCT03298763) is underway to access the efficacy of stem-cell-expressing TRAIL (MSCTRAIL) combined with chemotherapy in metastatic non-small cell lung cancer patients.…”

Section: Mscs In Os Therapymentioning

confidence: 99%

Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy

Sarhadi

Daddali

Seppänen‐Kaijansinkko

2021

IJMS

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Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.

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TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data

Cited by 33 publications

References 142 publications

Lipid Nanoparticles Decorated with TNF-Related Aptosis-Inducing Ligand (TRAIL) Are More Cytotoxic than Soluble Recombinant TRAIL in Sarcoma

Lipid Nanoparticles Decorated with TNF-Related Aptosis-Inducing Ligand (TRAIL) Are More Cytotoxic than Soluble Recombinant TRAIL in Sarcoma

Intracranial Delivery of Synthetic mRNA Using Common Transfection Reagent

Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy

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