| Autor: |
Simón-Gracia L; Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia., Loisel S; Université de Brest, Service Général des plateformes, Animalerie Commune, 29238 Brest, France., Sidorenko V; Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia., Scodeller P; Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia., Parizot C; Sorbonne Université, Inserm, CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département d'Immunologie, 75013 Paris, France., Savier E; Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Pitie-Salpetriere Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne University, 75013 Paris, France.; St Antoine Research Center (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne University, INSERM, 75012 Paris, France., Haute T; Université de Brest, Plateforme SyNanoVect, 29238 Brest, France., Teesalu T; Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.; Center for Nanomedicine, University of California Santa Barbara, 92037 Santa Barbara, California, United States., Rebollo A; Université de Paris, Inserm U1267, CNRS, Faculté de Pharmacie, 75006 Paris, France. |
| Abstrakt: |
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. The disease is characterized by the accumulation of tumoral B cells resulting from a defect of apoptosis. We have in vitro and in vivo preclinically validated a tumor-penetrating peptide (named TT1) coupled to an interfering peptide (IP) that dissociates the interaction between the serine/threonine protein phosphatase 2A (PP2A) from its physiological inhibitor, the oncoprotein SET. This TT1-IP peptide has an antitumoral effect on CLL, as shown by the increased survival of mice bearing xenograft models of CLL, compared to control mice. The peptide did not show toxicity, as indicated by the mouse body weight and the biochemical parameters, such as renal and hepatic enzymes. In addition, the peptide-induced apoptosis in vitro of primary tumoral B cells isolated from CLL patients but not of those isolated from healthy patients. Finally, the peptide had approximately 5 h half-life in human serum and showed pharmacokinetic parameters compatible with clinical development as a therapeutic peptide against CLL. |
