Studies on Deimmunization of Antileukaemic L-Asparaginase to have Reduced Clinical Immunogenicity--An in silico Approach

Pathology Oncology Research : POR
L N Ramya, Krishna Kanth Pulicherla

Abstract

Protein therapeutics, particularly of heterologous origin are shown to elicit immunogenic responses which result in adverse allergic reactions in spite of their promising clinical benefit. L-Asparaginase is one such well known chemotherapeutic agent that has enhanced the survival rates to 90 % in the treatment of acute lymphoblastic leukaemia for past 30 years. But the use of this enzyme is accompanied by hypersensitive reactions ranging from allergy to anaphylactic shock which have a drastic influence in treatment outcomes. Numerous attempts have been made to minimize the problems of immunogenicity, which remained as a major bottleneck in the treatment protocols. Conjugating the enzyme L- Asparaginase with PEG was successful as it has reduced the complications in therapy and frequency of injections (dosages), and thus became prominent in reducing the immunogenicity up to a certain extent. Keeping the bottlenecks in consideration during the development of therapeutics, the present study concentrates on engineering of protein as an alternative to the PEGylated enzyme, having reduced immunogenicity as an inbuilt character of protein by using in silico approaches. L-Asparaginase from Escherichia coli and Pectobacterium carotovorum...Continue Reading

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Citations

Sep 1, 2016·Journal of Immunology Research·Alison SmithFrank-Peter Theil
Oct 16, 2016·Expert Opinion on Biological Therapy·Surinder K Sharma, Kenneth D Bagshawe
Sep 26, 2019·World Journal of Microbiology & Biotechnology·Angela Beckett, David Gervais
Jan 25, 2018·Journal of Biomolecular Structure & Dynamics·Mahboubeh ZareiYounes Ghasemi
Sep 2, 2017·Scientific Reports·Coraline RigouinArnon Lavie
May 2, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Marcela Helena Gambim FonsecaRaphael Trevizani

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