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Current Applied Polymer Science


ISSN (Print): 2452-2716
ISSN (Online): 2452-2724

Review Article

Modified Asparaginase for Treatment of Cancer Historical Appraisal and Future Perspectives

Author(s): Luis Peña Icart*, Talita Stelling de Araújo, Marcius da Silva Almeida and Luís Maurício Trambaioli da Rocha e Lima*

Volume 6, Issue 1, 2023

Published on: 18 January, 2023

Page: [14 - 25] Pages: 12

DOI: 10.2174/2452271606666230104143806

Price: $65


Asparaginase (ASNase) is widely used as an important component of first-line treatment for acute lymphoblastic leukemia (ALL). Although it is associated with a high rate of complete remission (~93%), challenges remain due to several side effects ranging from immune reactions to severe toxicity, largely associated with its higher immunogenicity and glutamine coactivity. Innovative products have therefore been devised to minimise these adverse reactions while increasing the enzymes’ pharmacokinetic properties, stability, and efficacy. This review focuses on commercially available formulations and others that remain in development, discussing the most recent strategies for preparing alternative formulations of the enzyme to be less immunogenic and have low glutaminase coactivity by using site-specific mutagenesis, PEGylation, and encapsulation techniques.

Keywords: Asparaginase, bioconjugation, mutation, PEGylated, encapsulated humanized, acute lymphoblastic leukemia (ALL).

Graphical Abstract
Pinho PGD, Carvalho M. Pinto J. Cancer metabolomics 2018. MDPI 2019
Miranda-Filho A, Piñeros M, Ferlay J, Soerjomataram I, Monnereau A, Bray F. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol 2018; 5(1): e14-24.
[] [PMID: 29304322]
Nguyen HA, Su Y, Zhang JY, et al. A novel l -asparaginase with low l -glutaminase coactivity is highly efficacious against both t- and b-cell acute lymphoblastic leukemias in vivo. Cancer Res 2018; 78(6): 1549-60.
[] [PMID: 29343523]
Key statistics for acute lymphocytic leukemia (ALL). Cancer 2022. Available From : [
Lu XT. Therapeutic strategies for childhood high-risk acute lymphoblastic leukemia. Beijing Da Xue Xue Bao 2013; 45(2): 327-32.
[PMID: 23591360]
Schrappe M, Reiter A, Ludwig WD, et al. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: Results of trial ALL-BFM 90. Blood 2000; 95(11): 3310-22.
[PMID: 10828010]
Masetti R, Pession A. First-line treatment of acute lymphoblastic leukemia with pegasparaginase. Biologics 2009; 3: 359-68.
[PMID: 19707421]
Gerson SL, Caimi PF, William BM, Creger RJ. Pharmacology and molecular mechanisms of antineoplastic agents for hematologic malignancies hematology. Elsevier 2018; pp. 849-912.
Graham M. Pegaspargase: A review of clinical studies. Adv Drug Deliv Rev 2003; 55(10): 1293-302.
[] [PMID: 14499708]
Pieters R, Hunger SP, Boos J, et al. L-asparaginase treatment in acute lymphoblastic leukemia. Cancer 2011; 117(2): 238-49.
[] [PMID: 20824725]
El-Naggar NEA, Moawad H, El-Shweihy NM, El-Ewasy SM. Optimization of culture conditions for production of the anti-leukemic glutaminase free l-asparaginase by newly isolated streptomyces olivaceus neae-119 using response surface methodology. BioMed Res Int 2015; 2015: 1-17.
[] [PMID: 26180806]
Cecconello DK, Magalhães MR, Werlang ICR, Lee MLM, Michalowski MB, Daudt LE. Asparaginase: An old drug with new questions. Hematol Transfus Cell Ther 2020; 42(3): 275-82.
[] [PMID: 31801703]
Mitchell L, Hoogendoorn H, Giles AR, Vegh P, Andrew M. Increased endogenous thrombin generation in children with acute lymphoblastic leukemia: risk of thrombotic complications in L’Asparaginase-induced antithrombin III deficiency. Blood 1994; 83(2): 386-91.
[] [PMID: 8286739]
Nowak-Göttl U, Wolff JEA, Kuhn N, et al. Enhanced thrombin generation, P-von willebrand factor, P-fibrin D-dimer and P-plasminogen activator inhibitor 1: Predictive for venous thrombosis in asparaginase-treated children. Fibrinolysis 1994; 8: 63-5.
Rizzari C, Zucchetti M, Conter V, et al. L-asparagine depletion and L-asparaginase activity in children with acute lymphoblastic leukemia receiving i.m. or i.v. Erwinia C. or E. coli L-asparaginase as first exposure. Ann Oncol 2000; 11(2): 189-93.
[] [PMID: 10761754]
Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet 2008; 371(9617): 1030-43.
[] [PMID: 18358930]
Santos MO. Estimativa 2018: Incidência de câncer no brasil. Rev Bras Cancerol 2018; 64(1): 119-20.
Oliveira PD. Leukaemia prevalence worldwide: Raising aetiology questions. Lancet Haematol 2018; 5(1): e2-3.
[] [PMID: 29304323]
Earp Siqueira AS, Gonçalves JG, Xavier Mendonca PE, Elias Merhy E, Poirot Land MG. Economic impact analysis of cancer in the health system of Brazil: model based in public database. Health Sci J 2017; 11(4): 1.
Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma 2016; 57(4): 748-57.
[] [PMID: 26457414]
Emadi A, Zokaee H, Sausville EA. Asparaginase in the treatment of non-ALL hematologic malignancies. Cancer Chemother Pharmacol 2014; 73(5): 875-83.
[] [PMID: 24515335]
Arrivukkarasan S, Muthusivaramapandian M, Aravindan R, Viruthagiri T. Effect of medium composition and kinetic studies on extracellular and intracellular production of L-asparaginase from Pectobacterium carotovorum. Food Sci Technol Int 2010; 16(2): 115-25.
[] [PMID: 21339127]
Zuo S, Xue D, Zhang T, Jiang B, Mu W. Biochemical characterization of an extremely thermostable l-asparaginase from thermococcus gammatolerans EJ3. J Mol Catal, B Enzym 2014; 109: 122-9.
Whitecar JP Jr, Bodey GP, Harris JE, Freireich EJ. L-Asparaginase. N Engl J Med 1970; 282(13): 732-4.
[] [PMID: 4906449]
Yun MK, Nourse A, White SW, Rock CO, Heath RJ. Crystal structure and allosteric regulation of the cytoplasmic Escherichia coli L-asparaginase I. J Mol Biol 2007; 369(3): 794-811.
[] [PMID: 17451745]
Boos J, Werber G, Ahlke E, et al. Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparations. Eur J Cancer 1996; 32(9): 1544-50.
[] [PMID: 8911116]
Ortlund E, Lacount MW. Lacount §, Lewinski K, Lukasz L. Reactions of pseudomonas 7a glutaminase-asparaginase with diazo analogues of glutamine and asparagine result in unexpected covalent inhibitions and suggests an unusual catalytic triad Thr-Tyr-Glu. Biochemistry 2000; 39(6): 1199-204.
[] [PMID: 10684596]
Müller H, Boos J. Use of? -asparaginase in childhood ALL. Crit Rev Oncol Hematol 1998; 28(2): 97-113.
[] [PMID: 9768345]
Jones B, Holland JF, Glidewell O, et al. Optimal use of L-asparaginase (NSC-109229) in acute lymphocytic leukemia. Med Pediatr Oncol 1977; 3(4): 387-400.
[] [PMID: 337095]
Chand S, Mahajan RV, Prasad JP, et al. A comprehensive review on microbial l ‐asparaginase: Bioprocessing, characterization, and industrial applications. Biotechnol Appl Biochem 2020; 67(4): 619-47.
[] [PMID: 31954377]
Asselin B, Rizzari C. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring. Leuk Lymphoma 2015; 56(8): 2273-80.
[] [PMID: 25586605]
Völler S, Pichlmeier U, Zens A, Hempel G. Pharmacokinetics of recombinant asparaginase in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol 2018; 81(2): 305-14.
[] [PMID: 29204688]
Plourde PV, Jeha S, Hijiya N, et al. Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate‐use trial. Pediatr Blood Cancer 2014; 61(7): 1232-8.
[] [PMID: 24436152]
Li RJ, Jin R, Liu C, et al. FDA approval summary: Calaspargase pegol-mknl for treatment of acute lymphoblastic leukemia in children and young adults. Clin Cancer Res 2020; 26(2): 328-31.
[] [PMID: 31444252]
Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: Pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist 2007; 12(8): 991-8.
[] [PMID: 17766659]
Costa-Silva TA, Costa IM, Biasoto HP, et al. Critical overview of the main features and techniques used for the evaluation of the clinical applicability of L-asparaginase as a biopharmaceutical to treat blood cancer. Blood Rev 2020; 43: 100651.
[] [PMID: 32014342]
Gadelha MIP. Monitoring asparaginase activity. Lancet Oncol 2018; 19(11): e575.
[] [PMID: 30507478]
Kumar K, Kaur J, Walia S, Pathak T, Aggarwal D. l -asparaginase: An effective agent in the treatment of acute lymphoblastic leukemia. Leuk Lymphoma 2014; 55(2): 256-62.
[] [PMID: 23662993]
Labrou NE, Papageorgiou AC, Avramis VI. Structure-function relationships and clinical applications of l-asparaginases. Curr Med Chem 2010; 17: 2183-95.
[] [PMID: 20423302]
Silverman LB, Supko JG, Stevenson KE, et al. Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Blood 2010; 115(7): 1351-3.
[] [PMID: 20007809]
Angiolillo AL, Schore RJ, Devidas M, et al. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: Results from Children’s Oncology Group Study AALL07P4. J Clin Oncol 2014; 32(34): 3874-82.
[] [PMID: 25348002]
Marini BL, Perissinotti AJ, Bixby DL, Brown J, Burke PW. Catalyzing improvements in ALL therapy with asparaginase. Blood Rev 2017; 31(5): 328-38.
[] [PMID: 28697948]
Salzer W, Bostrom B, Messinger Y, Perissinotti AJ, Marini B. Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia. Leuk Lymphoma 2018; 59(8): 1797-806.
[] [PMID: 29045165]
Rathod S, Ramsey M, Relling MV, Finkelman FD, Fernandez CA. Hypersensitivity reactions to asparaginase in mice are mediated by anti-asparaginase IgE and IgG and the immunoglobulin receptors FcεRI and FcγRIII. Haematologica 2019; 104(2): 319-29.
[] [PMID: 30237274]
van der Sluis IM, Vrooman LM, Pieters R, et al. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica 2016; 101(3): 279-85.
[] [PMID: 26928249]
Avramis VI, Sencer S, Periclou AP, et al. A randomized comparison of nativeEscherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: A Children’s Cancer Group study. Blood 2002; 99(6): 1986-94.
[] [PMID: 11877270]
Panosyan EH, Seibel NL, Martin-Aragon S, et al. Asparaginase antibody and asparaginase activity in children with higher-risk acute lymphoblastic leukemia: Children’s Cancer Group Study CCG-1961. J Pediatr Hematol Oncol 2004; 26(4): 217-26.
[] [PMID: 15087948]
Woo MH, Hak LJ, Storm MC, et al. Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia. J Clin Oncol 2000; 18(7): 1525-32.
[] [PMID: 10735901]
Avramis VI, Martin-Aragon S, Avramis EV, Asselin BL. Pharmacoanalytical assays of Erwinia asparaginase (erwinase) and pharmacokinetic results in high-risk acute lymphoblastic leukemia (HR ALL) patients: Simulations of erwinase population PK-PD models. Anticancer Res 2007; 27(4C): 2561-72.
[PMID: 17695416]
Avramis VI, Panosyan EH. Pharmacokinetic/pharmacodynamic relationships of asparaginase formulations: The past, the present and recommendations for the future. Clin Pharmacokinet 2005; 44(4): 367-93.
[] [PMID: 15828851]
Larson RA, Fretzin MH, Dodge RK, Schiffer CA. Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia. Leukemia 1998; 12(5): 660-5.
[] [PMID: 9593262]
Hoogerbrugge N, Jansen H, Hoogerbrugge PM. Transient hyperlipidemia during treatment of ALL with L-asparaginase is related to decreased lipoprotein lipase activity. Leukemia 1997; 11(8): 1377-9.
[] [PMID: 9264396]
Tong WH, Pieters R, de Groot-Kruseman HA, et al. The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia. Haematologica 2014; 99(11): 1716-21.
[] [PMID: 25150254]
Heitink-Pollé KMJ, Prinsen BHCMT, de Koning TJ, van Hasselt PM, Bierings MB. High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. JIMD Rep •••; 7: 103-8.
[] [PMID: 23430503]
Asselin BL, Fisher V. Impact of clinical and subclinical hypersensitivity to asparaginase in acute lymphoblastic leukemia. Clin J Oncol Nurs 2014; 18(6): E107-12.
[] [PMID: 25427712]
Grigoryan RS, Panosyan EH, Seibel NL, Gaynon PS, Avramis IA, Avramis VI. Changes of amino acid serum levels in pediatric patients with higher-risk acute lymphoblastic leukemia (CCG-1961).in vivo 2004; 18(2): 107-2.
[PMID: 15113036]
Raja RA, Schmiegelow K, Frandsen TL. Asparaginase-associated pancreatitis in children. Br J Haematol 2012; 159(1): 18-27.
[] [PMID: 22909259]
Rank CU, Wolthers BO, Grell K, et al. Asparaginase-associated pancreatitis in acute lymphoblastic leukemia: Results from the nopho all2008 treatment of patients 1-45 years of age. J Clin Oncol 2020; 38(2): 145-54.
[] [PMID: 31770057]
Durden DL, Salazar AM, Distasio JA. Kinetic analysis of hepatotoxicity associated with antineoplastic asparaginases. Cancer Res 1983; 43(4): 1602-5.
[PMID: 6339039]
Fonseca MHG, Fiúza T da S, Morais S. Circumventing the side effects of L-asparaginase. Biomed Pharmacother 2021; 139: 111616.
[] [PMID: 33932739]
Nussbaum V, Lubcke N, Findlay R. Hyperammonemia secondary to asparaginase: A case series. J Oncol Pharm Pract 2016; 22(1): 161-4.
[] [PMID: 25245038]
Damodaran VB, Fee C. Protein PEGylation: An overview of chemistry and process considerations. Eur Pharm Rev 2010; 15: 18-26.
Jevševar S, Kunstelj M, Porekar VG. PEGylation of therapeutic proteins. Biotechnol J 2010; 5(1): 113-28.
[] [PMID: 20069580]
Avramis VI, Tiwari PN. Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. Int J Nanomedicine 2006; 1(3): 241-54.
[PMID: 17717965]
Keating MJ, Holmes R, Lerner S, Ho DH. L-asparaginase and PEG asparaginase--past, present, and future. Leuk Lymphoma 1993; 10 ((sup1)(Suppl.)): 153-7.
[] [PMID: 8481665]
Vrooman LM, Blonquist TM, Supko JG, et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia/lymphoma: Results of DFCI 11-001. J Clin Oncol 2019; 37(15) (Suppl.): 10006-6.
Brandenburg G, Poppenborg S, Radcke C, et al. 10 - Challenges in the analytical characterization of pegylated asparaginase polymer-protein conjugates. Elsevier 2020; pp. 205-31.
Lew G. Space for calaspargase? a new asparaginase for acute lymphoblastic leukemia. Clin Cancer Res 2020; 26(2): 325-7.
[] [PMID: 31641006]
Shrivastava A, Khan AA, Khurshid M, Kalam MA, Jain SK, Singhal PK. Recent developments in l-asparaginase discovery and its potential as anticancer agent. Crit Rev Oncol Hematol 2016; 100: 1-10.
[] [PMID: 25630663]
Egler RA, Ahuja SP, Matloub Y. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother 2016; 7(2): 62-71.
[] [PMID: 27440950]
Burke MJ. How to manage asparaginase hypersensitivity in acute lymphoblastic leukemia. Future Oncol 2014; 10(16): 2615-27.
[] [PMID: 24983955]
Figueiredo L, Cole PD, Drachtman RA. Asparaginase erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase. Expert Rev Hematol 2016; 9(3): 227-34.
[] [PMID: 26765930]
Chien WW, Allas S, Rachinel N, et al. Pharmacology, immunogenicity, and efficacy of a novel pegylated recombinant Erwinia chrysanthemi-derived L-asparaginase. Invest New Drugs 2014; 32(5): 795-805.
[] [PMID: 24829072]
Derst C, Henseling J, Röhm KH. Engineering the substrate specificity of Escherichia coli asparaginase II. Selective reduction of glutaminase activity by amino acid replacements at position 248. Protein Sci 2000; 9(10): 2009-17.
[] [PMID: 11106175]
Offman MN, Krol M, Patel N, et al. Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity. Blood 2011; 117(5): 1614-21.
[] [PMID: 21106986]
Melik-Nubarov NS, Grozdova ID, Lomakina GY, et al. PEGylated recombinant L-asparaginase from Erwinia carotovora: Production, properties, and potential applications. Prikl Biokhim Mikrobiol 2017; 53(2): 164-72.
[PMID: 29508977]
Allas S, Sahakian P, Fichtner I, Abribat T. Immunogenicity profile in mice of a pegylated recombinant Erwinia chrysanthemi-derived l-asparaginase. Blood 2009; 114(22): 2034-4.
Meneguetti GP, Santos JHPM, Obreque KMT, et al. Novelsite-specific PEGylated L-asparaginase. PLoS One 2019; 14: e0211951.
[] [PMID: 30753228]
Ramirez-Paz J, Saxena M, Delinois LJ, et al. Thiol-maleimide poly(ethylene glycol) crosslinking of L-asparaginase subunits at recombinant cysteine residues introduced by mutagenesis. PLoS One 2018; 13(7): e0197643.
[] [PMID: 30052638]
Manuela Gaspar M, Blanco D, Cruz MEM, José Alonso M. Formulation of l-asparaginase-loaded poly(lactide-co-glycolide) nanoparticles: influence of polymer properties on enzyme loading, activity and in vitro release. J Control Release 1998; 52(1-2): 53-62.
[] [PMID: 9685935]
Wolf M, Wirth M, Pittner F, Gabor F. Stabilisation and determination of the biological activity of l-asparaginase in poly(d,l-lactide-co-glycolide) nanospheres. Int J Pharm 2003; 256(1-2): 141-52.
[] [PMID: 12695020]
Tinoco A, Ribeiro A, Oliveira C, Parpot P, Gomes A, Cavaco-Paulo A. Albumin/asparaginase capsules prepared by ultrasound to retain ammonia. Appl Microbiol Biotechnol 2016; 100(22): 9499-508.
[] [PMID: 27314846]
Rigouin C, Nguyen HA, Schalk AM, Lavie A. Discovery of human-like L-asparaginases with potential clinical use by directed evolution. Sci Rep 2017; 7(1): 10224.
[] [PMID: 28860480]
Belviso S, Iuliano R, Amato R, Perrotti N, Menniti M. The human asparaginase enzyme (ASPG) inhibits growth in leukemic cells. PLoS One 2017; 12(5): e0178174.
[] [PMID: 28542249]
Narta UK, Kanwar SS, Azmi W. Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia. Crit Rev Oncol Hematol 2007; 61(3): 208-21.
[] [PMID: 17011787]
Chiu M, Tardito S, Pillozzi S, et al. Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts. Br J Cancer 2014; 111(6): 1159-67.
[] [PMID: 25072259]
Parmentier JH, Maggi M, Tarasco E, Scotti C, Avramis VI, Mittelman SD. Glutaminase activity determines cytotoxicity of l-asparaginases on most leukemia cell lines. Leuk Res 2015; 39(7): 757-62.
[] [PMID: 25941002]
Fung MKL, Chan GCF. Drug-induced amino acid deprivation as strategy for cancer therapy. J Hematol Oncol 2017; 10(1): 144.
[] [PMID: 28750681]
Chan WK, Lorenzi PL, Anishkin A, et al. The glutaminase activity of l-asparaginase is not required for anticancer activity against ASNS-negative cells. Blood 2014; 123(23): 3596-606.
[] [PMID: 24659632]
Ardalan N, Mirzaie S, Sepahi AA, Khavari-Nejad RA. Novel mutant of Escherichia coli asparaginase II to reduction of the glutaminase activity in treatment of acute lymphocytic leukemia by molecular dynamics simulations and QM-MM studies. Med Hypotheses 2018; 112: 7-17.
[] [PMID: 29447943]
Battiston Loureiro C, Silva Borges K, Faria Andrade A, Gonzaga Tone L, Said S. Purification and biochemical characterization of native and pegylated form of L-asparaginase from aspergillus terreus and evaluation of its antiproliferative activity. Adv Microbiol 2012; 2(2): 138-45.
Chien WW, Lebeux C, Rachinel N, et al. Anti-leukemic activity of a novel pegylated recombinant Erwinia chrysanthemi-derived L-asparaginase on lymphoid cell lines and leukemia-bearing mouse models. Blood 2012; 120(21): 2571-1.
Pisal DS, Kosloski MP, Balu-Iyer SV. Delivery of therapeutic proteins. J Pharm Sci 2010; 99(6): 2557-75.
[] [PMID: 20049941]
Abe M, Akbarzaderaleh P, Hamachi M, Yoshimoto N, Yamamoto S. Interaction mechanism of mono-PEGylated proteins in electrostatic interaction chromatography. Biotechnol J 2010; 5(5): 477-83.
[] [PMID: 20440716]
Nair D, Podgórski M, Chatani S, et al. The thiol‐michael addition click reaction: a powerful and widely used tool in materials chemistry. Chem Mater 2014; 26(1): 724-44.
Soares AL, Guimarães GM, Polakiewicz B, Pitombo RNM, Abrahão-Neto J. Effects of polyethylene glycol attachment on physicochemical and biological stability of E. coli l-asparaginase. Int J Pharm 2002; 237(1-2): 163-70.
[] [PMID: 11955814]
Edman P, Sjöholm I. Acrylic microspheres in vivo V: Immunological properties of immobilized asparaginase in microparticles. J Pharm Sci 1982; 71(5): 576-80.
[] [PMID: 6212669]
Baran ET, Ozer N, Hasirci V. in vivo half life of nanoencapsulated L-asparaginase. J Mater Sci Mater Med 2002; 13: 1113-21.
[] [PMID: 15348652]
Vasudev SS, Ahmad S, Parveen R, et al. Formulation of PEG-ylated L-asparaginase loaded poly (lactide-co-glycolide) nanoparticles: influence of Pegylation on enzyme loading, activity and in vitro release. Pharmazie 2011; 66(12): 956-60.
[PMID: 22312702]
Karamitros CS, Konrad M. Human 60-kDa lysophospholipase contains an N-terminal L-asparaginase domain that is allosterically regulated by L-asparagine. J Biol Chem 2014; 289(19): 12962-75.
[] [PMID: 24657844]
Schalk AM, Nguyen HA, Rigouin C, Lavie A. Identification and structural analysis of an L-asparaginase enzyme from guinea pig with putative tumor cell killing properties. J Biol Chem 2014; 289(48): 33175-86.
[] [PMID: 25320094]
Roth G, Nunes JES, Rosado LA, et al. Recombinant Erwinia carotovora l-asparaginase II production in Escherichia coli fed-batch cultures. Braz J Chem Eng 2013; 30(2): 245-56.
Kidd JG. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. I. Course of transplanted cancers of various kinds in mice and rats given guinea pig serum, horse serum, or rabbit serum. J Exp Med 1953; 98(6): 565-82.
[] [PMID: 13109110]

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