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In vivo stabilization of a less toxic asparaginase variant leads to a durable antitumor response in acute leukemia Universiteit Gent KU Leuven

Maaike Van Trimpont, Amanda M. Schalk, Yanti De Visser, Hien Anh Nguyen, Lindy Reunes, Katrien Vandemeulebroecke, Evelien Peeters, Ying Su, Hyun Lee, Philip L. Lorenzi, et al.
Asparagine is a non-essential amino acid since it can either be taken up via the diet or synthesized by asparagine synthetase. Acute lymphoblastic leukemia (ALL) cells do not express asparagine synthetase or express it only minimally, which makes them completely dependent on extracellular asparagine for their growth and survival. This dependency makes ALL cells vulnerable to treatment with L-asparaginase, an enzyme that hydrolyzes asparagine. To ...

Safety evaluation of the food enzyme asparaginase from the genetically modified Aspergillus oryzae strain NZYM-OA. Instituut voor Landbouw-, Visserij- en Voedingsonderzoek

Lieve Herman

The food enzyme asparaginase (l-asparagine amidohydrolase; EC 3.5.1.1) is produced with the genetically modified microorganism Aspergillus oryzae strain NZYM-OA by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in various food manufacturing processes to prevent acrylamide formation. Dietary exposure to the ...

Novel insights on the use of L-asparaginase as an efficient and safe anti-cancer therapy Universiteit Gent KU Leuven

Maaike Van Trimpont, Evelien Peeters, Yanti De Visser, Amanda M. Schalk, Veerle Mondelaers, Barbara De Moerloose, Arnon Lavie, Tim Lammens, Steven Goossens, Pieter Van Vlierberghe, et al.
Simple Summary L-asparaginase (L-ASNase) therapy is key for achieving the very high cure rate of pediatric acute lymphoblastic leukemia (ALL), yet its use is mostly confined to this indication. One main reason preventing the expansion of today's FDA-approved L-ASNases to solid cancers is their high toxicity and side effects, which become especially challenging in adult patients. The design of optimized L-ASNase molecules provides opportunities ...

Preserving catalytic activity and enhancing biochemical stability of the therapeutic enzyme asparaginase by biocompatible multilayered polyelectrolyte microcapsules Universiteit Gent

Christos S Karamitros, Alexey M Yashchenok, Helmuth Möhwald, Andre Skirtach, Manfred Konrad
The present study focuses on the formation of microcapsules containing catalytically active L-asparaginase (L-ASNase), a protein drug of high value in antileukemic therapy. We make use of the layer-by-layer (LbL) technique to coat protein-loaded calcium carbonate (CaCO3) particles with two or three poly dextran/poly-L-arginine-based bilayers. To achieve high loading efficiency, the CaCO3 template was generated by coprecipitation with the enzyme. ...

Safety evaluation of the food enzyme asparaginase from the genetically modified Aspergillus niger strain ASP. Instituut voor Landbouw-, Visserij- en Voedingsonderzoek

Lieve Herman
The food enzyme asparaginase (l-asparagine amidohydrolase; EC 3.5.1.1) is produced with the genetically modified Aspergillus niger strain ASP by DSM Food Specialties B.V. The genetic modifications do not give rise to safety concerns. The food enzyme was considered free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in the prevention of acrylamide formation in foods and in the processing of yeast ...

Prolonged versus standard native E-coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 Universiteit Antwerpen KU Leuven Universiteit Gent

Veerle Mondelaers, Stefan Suciu, Barbara De Moerloose, Alina Ferster, Francoise Mazingue, Genevieve Plat, Karima Yakouben, Anne Uyttebroeck, Patrick Lutz, Vitor Costa, et al.
Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of non-very high-risk patients by comparing prolonged (long-asparaginase) versus standard (short-asparaginase) native E. coli asparaginase treatment in a randomized part of the phase III 58951 trial of the European Organization for Research and Treatment ...

Hypersensitivity to Pegylated E.coli asparaginase as first-line treatment in contemporary paediatric acute lymphoblastic leukaemia protocols : a meta-analysis of the Ponte di Legno Toxicity working group Universiteit Gent

Leiah J. Brigitha, Marta Fiocco, Rob Pieters, Birgitte K. Albertsen, Gabriele Escherich, Elixabet Lopez-Lopez, Veerle Mondelaers, Ajay Vora, Lynda Vrooman, Kjeld Schmiegelow, et al.
Background: Hypersensitivity reactions to asparaginase challenge its use and occur frequently (30-75%) after native Escherichia Coli (E.coli) asparaginase. Comparison of inci-dence of allergic reactions to pegylated E.coli asparaginase (PEGasparaginase) across contem-porary paediatric acute lymphoblastic leukaemia (ALL) protocols is lacking. Method and patients: Questionnaires were sent to all members of the international ALL Ponte di Legno ...

Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium Universiteit Antwerpen Universiteit Gent KU Leuven Vrije Universiteit Brussel

Veerle Mondelaers, Alina Ferster, Anne Uyttebroeck, Benedicte Brichard, Juttevan Werff der ten Bosch, Koenraad Norga, Nadine Francotte, Caroline Piette, Katrien Vandemeulebroecke, Charlotte Verbeke, et al.
Asparaginase (ASNase) is an important anti-leukaemic drug in the treatment of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL). A substantial proportion of patients develop hypersensitivity reactions with anti-ASNase neutralising antibodies, resulting in allergic reactions or silent inactivation (SI), and characterised by inactivation and rapid clearance of ASNase. We report results of a prospective, real-time ...

Histologic Analysis of Testes from Prepubertal Patients Treated with Chemotherapy Associates Impaired Germ Cell Counts with Cumulative Doses of Cyclophosphamide, Ifosfamide, Cytarabine, and Asparaginase Vrije Universiteit Brussel

Jose V Medrano, D Hervás, T Vilanova-Pérez, A Navarro-Gomezlechon, Ellen Goossens, A Pellicer, MDM Andrés, E Novella-Maestre

Cryopreservation of immature testicular tissue is an experimental strategy for the preservation of fertility in prepubertal boys that will be subjected to a gonadotoxic onset, as is the case of oncologic patients. Therefore, the objective of this study was to assess the impact of chemotherapeutic treatments on the testicular histologic phenotype in prepubertal patients. A total of 56 testicular tissue samples from pediatric patients between 0 ...