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Can recombinant technology address asparaginase Erwinia chrysanthemi shortages?
Author(s) -
Maese Luke,
Rizzari Carmelo,
Coleman Russell,
Power Austin,
Sluis Inge,
Rau Rachel E.
Publication year - 2021
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.29169
Subject(s) - asparaginase , medicine , recombinant dna , erwinia , escherichia coli , microbiology and biotechnology , lymphoblastic leukemia , leukemia , immunology , biochemistry , biology , gene
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Bacterial L‐asparaginase has played an important role in ALL treatment for several decades; however, hypersensitivity reactions to Escherichia coli ‐derived asparaginases often preclude their use. Inability to receive asparaginase due to hypersensitivities is associated with poor patient outcomes. Erwinia chrysanthemi ‐derived asparaginase (ERW) is an effective, non‐cross‐reactive treatment option, but is limited in supply. Consequently, alternative asparaginase preparations are needed to ensure asparaginase availability for patients with hypersensitivities. Recombinant technology can potentially address this unmet need by programming cells to produce recombinant asparaginase. JZP‐458, a recombinant Erwinia asparaginase derived from a novel Pseudomonas fluorescens expression platform with no immunologic cross‐reactivity to E. coli ‐derived asparaginases, has the same primary amino acid sequence as ERW, with comparable activity based on in vitro measurements. The efficient manufacturing of JZP‐458 would provide an additional asparaginase preparation for patients with hypersensitivities.

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