Downstream process and evaluation of the concomitant impact of a recombinant glycosylated L-asparaginase on leukemic cancer cells and the bone marrow tumor microenvironment
| Primer Autor |
Calle, Yolanda
|
| Co-autores |
Kleingesinds, Eduardo Krebs
Parizotto, Leticia de Almeida
Effer, Brian
Monteiro, Gisele
Long, Paul F.
Arroyo-Berdugo, Yoana
Behrends, Volker
Esposito, Maria Teresa
Pessoa-Jr, Adalberto
|
| Título |
Downstream process and evaluation of the concomitant impact of a recombinant glycosylated L-asparaginase on leukemic cancer cells and the bone marrow tumor microenvironment
|
| Editorial |
ELSEVIER SCI LTD
|
| Revista |
PROCESS BIOCHEMISTRY
|
| Lenguaje |
en
|
| Resumen |
L-asparaginase (L-ASNase) is a life-saving medication used in the treatment of Acute Lymphoblastic Leukemia (ALL) which affects over 60,000 people yearly. However, L-ASNase still requires improvement since up to 60% of the patients develop hypersensitivity due to its immunogenicity. To address this issue, this work describes the downstream process of an L-ASNase from Erwinia chrysanthemi expressed extracellularly by Pichia pastoris with human-like glycosylation pattern and its further impact on leukemic cells co-cultured with bone marrow (BM) cytoprotective stromal cells. After size exclusion chromathography, a final yield of 54.93% was achieved and the proteomics analyses confirmed the attainment of an extremely pure enzyme. Glycosylated L-ASNase induced the complete inhibition of the proliferation of ALL and Acute Myeloid Leukemia (AML) cell lines tested, independently of the presence of BM stromal cells. However, the cytotoxic efficacy (induction of apoptosis) of glycosylated L-ASNase varied across cell lines, with ALL cell lines showing the most sensitivity. Additionally, the proapoptotic effect of glycosylated L-ASNase was partially inhibited by BM stromal cells. Taken together, our data warrant further investigations for the use of glycosylated L-ASNase against ALL and AML that should take into consideration the mechanisms of resistance mediated by the BM stroma for improved efficacy.
|
| Fecha Publicación |
2023
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| Tipo de Recurso |
artículo original
|
| doi |
10.1016/j.procbio.2023.06.006
|
| Formato Recurso |
PDF
|
| Palabras Claves |
L-ASNase
Leukemia
Pichia pastoris
Protein purification
Cross-flow filtration
Tumour microenvironment
|
| Ubicación del archivo | |
| Categoría OCDE |
Bioquímica y Biología Molecular
Biotecnología y Microbiología Aplicada
Ingeniería
|
| Materias |
L-ASNasa
Leucemia
Pichia pastoris
Purificación de proteínas
Filtración de flujo cruzado
Microambiente tumoral
|
| Página de inicio (Recomendado-único) |
41.0
|
| Página final (Recomendado-único) |
51
|
| Identificador del recurso (Mandatado-único) |
artículo original
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| Versión del recurso (Recomendado-único) |
versión publicada
|
| License |
CC BY 4.0
|
| Condición de la licencia (Recomendado-repetible) |
CC BY 4.0
|
| Derechos de acceso |
acceso abierto
|
| Access Rights |
acceso abierto
|
| Id de Web of Science |
WOS:001028014900001
|
| ISSN |
1359-5113
|
| Tipo de ruta |
verde# hibrida
|
| Categoría WOS |
Bioquímica y Biología Molecular
Biotecnología y Microbiología Aplicada
Ingeniería
|
| Referencia del Financiador (Mandatado si es aplicable-repetible) |
ANID-FONDECYT 3210142
CONICYT 21150288
FAPESP 2013/08617-7
FAPESP 2015/07749-2
FAPESP 2017/20384-9
FAPESP 2017/25065-9
FAPESP 2018/15104-0
FAPESP 2018/03734-9
FAPESP 2019/06919-2
UFRO DI12-PEO1 EXE12-0004
CNPQ 309224/2019-5
CRUK C34579/A20784
ANID FONDECYT 3210142
ANID CONICYT 21150288
CNPq 309224/2019-5
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