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

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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.

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Acknowledgements

This study was supported by Carife Foundation and by a grant from “Programma di Ricerca Regione-Università 2007/2009” (Regione Emilia Romagna) (to PS).

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Correspondence to Paola Secchiero.

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Gonelli, A., Radillo, O., Drioli, S. et al. Pegylated TRAIL retains anti-leukemic cytotoxicity and exhibits improved signal transduction activity with respect to TRAIL. Invest New Drugs 30, 828–832 (2012). https://doi.org/10.1007/s10637-010-9599-8

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  • DOI: https://doi.org/10.1007/s10637-010-9599-8

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