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However, nErA has a short in vivo half-life requiring frequent dosing schedules in patients. In this study, nErA was covalently conjugated to PEG molecules with the aim of extending its half-life in vivo. <jats:italic>Methods<\/jats:italic>. Firstly, efficacy of this novel product PEG-nErA was investigated on human ALL cell lines (Jurkat, CCRF-CEM and CCRF-HSB2), in vitro. Secondly, its pharmacokinetic (PK) and pharmacodynamic (PD) characteristics were determined, in vivo (12 rats in each group).\u00a0<jats:italic>Results<\/jats:italic>. It was found that the specific activity (U\/mg of enzyme) and the kinetic constant (K<jats:sub>M<\/jats:sub>) of nErA remained unaltered post PEGylation. PEG-nErA was shown to have similar cytotoxicity to nErA (IC<jats:sub>50<\/jats:sub>: 0.06\u20130.17 U\/mL) on human ALL cell lines, in vitro<jats:italic>.<\/jats:italic> Further, when compared to nErA, PEG-nErA showed a significantly improved half-life\u00a0in vivo, which meant that L-Asparagine (Asn) levels in plasma remained depleted for up to 25\u00a0days with a four-fold lower dose (100 U\/kg) compared with 72\u00a0h for nErA at 400 U\/kg dose. <jats:italic>Conclusion<\/jats:italic>.\u00a0Overall, this next generation product PEG-nErA (with improved PK and PD characteristics compared to nErA)\u00a0would bring a significant advantage to the therapeutic needs of ALL patients and should be further explored in clinical trials.<\/jats:p>","DOI":"10.1007\/s10637-021-01173-8","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T11:03:09Z","timestamp":1630494189000},"page":"21-29","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Improved pharmacokinetic and pharmacodynamic profile of a novel PEGylated native Erwinia chrysanthemi L-Asparaginase"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-5657","authenticated-orcid":false,"given":"Tapasvi","family":"Modi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Gervais","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"1173_CR1","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1046\/j.1365-2141.2000.02015.x","volume":"109","author":"A Dubbers","year":"2000","unstructured":"Dubbers A, Wurthwein G, Muller HJ, Schulze-Westhoff P, Winkelhorst M, Kurzknabe E et al (2000) Asparagine synthetase activity in paediatric acute leukaemias: AML-M5 subtype shows lowest activity. 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