PMID- 24829072
OWN - NLM
STAT- MEDLINE
DCOM- 20150609
LR  - 20211021
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 32
IP  - 5
DP  - 2014 Oct
TI  - Pharmacology, immunogenicity, and efficacy of a novel pegylated recombinant 
      Erwinia chrysanthemi-derived L-asparaginase.
PG  - 795-805
LID - 10.1007/s10637-014-0102-9 [doi]
AB  - Bacterial L-asparaginase (ASNase), hydrolyzing L-asparagine (Asn), is an 
      indispensable component used in the treatment of acute lymphoblastic leukemia 
      (ALL) and certain lymphoma entities. Native Erwinia chrysanthemi-derived ASNase 
      (n-crisantaspase) has been approved as a second-line drug for treating patients 
      exhibiting allergy syndromes to native and pegylated Escherichia coli-derived 
      ASNase (EC-ASNase). However, it still induces hypersensitivity in at least 17 % 
      of treated patients. In the present study, we investigated the pharmacological 
      activity, immunogenicity and anti-leukemic activity of a new pegylated 
      recombinant crisantaspase (PEG-r-crisantaspase). The results demonstrate that 
      when compared to n-crisantaspase in vivo, PEG-r-crisantaspase maintains a 
      complete depletion of plasma Asn for up to 72 h with a 50-fold lower dose. In 
      mice receiving PEG-r-crisantaspase, specific antibodies against the enzyme were 
      undetectable, indicating a lower immunogenicity of the pegylated enzyme. In 
      vitro, PEG-r-crisantaspase exhibits similar cytotoxic effects (EC50 < 5 x 10(-4) 
      U/mL for the most sensitive cell lines) to n-crisantaspase on various leukemia 
      and lymphoma cells and was shown to be more efficient than EC-ASNase. Three 
      repeated PEG-r-crisantaspase injections (2-20 U/Kg) prevented leukemia 
      development in leukemia-bearing mice for 17 days and significantly prolonged 
      animal survival to 7-12 days. Therefore, PEG-r-crisantaspase appears to be a 
      promising drug candidate for ALL treatment and should be further explored in 
      experimental and clinical trials.
FAU - Chien, Wei-Wen
AU  - Chien WW
AD  - Universite Claude Bernard Lyon 1, UMR 5239, CNRS, ENS, HCL, Faculte de Medecine 
      Lyon Sud Equipe du Pr. Gilles Salles "Pathologie des cellules lymphoides" 165 
      Chemin du Grand Revoyet, 69921, BP12, Oullins, France.
FAU - Allas, Soraya
AU  - Allas S
FAU - Rachinel, Nicolas
AU  - Rachinel N
FAU - Sahakian, Pierre
AU  - Sahakian P
FAU - Julien, Michel
AU  - Julien M
FAU - Le Beux, Celine
AU  - Le Beux C
FAU - Lacroix, Claire-Emmanuelle
AU  - Lacroix CE
FAU - Abribat, Thierry
AU  - Abribat T
FAU - Salles, Gilles
AU  - Salles G
LA  - eng
PT  - Journal Article
DEP - 20140515
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antibodies)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Animals
MH  - Antibodies/blood
MH  - *Antineoplastic Agents/chemistry/immunology/pharmacology/therapeutic use
MH  - *Asparaginase/chemistry/immunology/pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Dickeya chrysanthemi
MH  - Female
MH  - Humans
MH  - Mice
MH  - Polyethylene Glycols/chemistry
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood/drug therapy
MH  - Recombinant Proteins/chemistry/immunology/pharmacology/therapeutic use
MH  - Treatment Outcome
MH  - Xenograft Model Antitumor Assays
EDAT- 2014/05/16 06:00
MHDA- 2015/06/10 06:00
CRDT- 2014/05/16 06:00
PHST- 2014/01/21 00:00 [received]
PHST- 2014/04/09 00:00 [accepted]
PHST- 2014/05/16 06:00 [entrez]
PHST- 2014/05/16 06:00 [pubmed]
PHST- 2015/06/10 06:00 [medline]
AID - 10.1007/s10637-014-0102-9 [doi]
PST - ppublish
SO  - Invest New Drugs. 2014 Oct;32(5):795-805. doi: 10.1007/s10637-014-0102-9. Epub 
      2014 May 15.