Pegylated TRAIL retains anti-leukemic cytotoxicity and exhibits improved signal transduction activity with respect to TRAIL

• Published in: Investigational new drugs Vol. 30; no. 2; pp. 828 - 832
• Main Authors: Gonelli, Arianna, Radillo, Oriano, Drioli, Sara, Rimondi, Erika, Secchiero, Paola, Maria Bonora, Gian
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.04.2012; Springer Nature B.V
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Bone marrow; Cancer; Cancer therapies; Caspase 3 - metabolism; Cell Movement - drug effects; Clinical trials; Cytotoxicity; Dose-Response Relationship, Drug; Experiments; Genetic engineering; HL-60 Cells; Humans; Kinases; Leukemia; Leukemia - metabolism; Leukemia - pathology; Maternal & child health; Medicine; Medicine & Public Health; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Oncology; Pharmacokinetics; Pharmacology; Pharmacology/Toxicology; Phosphorylation; Polyethylene Glycols - pharmacology; Proteins; Recombinant Fusion Proteins - pharmacology; Short Report; Signal transduction; Signal Transduction - drug effects; Stem cells; Studies; Time Factors; TNF-Related Apoptosis-Inducing Ligand - pharmacology; Tumor necrosis factor-TNF; Italy; Signal transduction; Pegylation; TRAIL
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-010-9599-8

Summary To improve the pharmacokinetic profile of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) an N-terminal specific pegylation was performed to generate pegylated TRAIL (PEG-TRAIL). In in vitro experiments, we found that although PEG-TRAIL was slightly less efficient than recombinant TRAIL in promoting leukemic cell apoptosis, it showed an improved ability to promote migration of bone-marrow mesenchymal stem cells and to elicit the ERK1/2 intracellular signal transduction pathway. Overall, these data suggest that TRAIL pegylation retains, or even enhances, the biological activities of TRAIL relevant for its therapeutic applications.