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It affects lymphoid progenitor cells, leading to overproduction of immature B\u2010 or T\u2010cells. ALL cells rely on asparagine for survival. Therefore, the addition of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010asparaginase (ASNase), an enzyme that depletes asparagine, to the ALL chemotherapy backbone has dramatically improved treatment outcomes. However, marketed formulations of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010ASNase, all derived from bacteria, with or without polyethylene glycol (PEG) modification, cause allergic reactions to the enzyme or to PEG, impacting treatment efficacy. Herein, existing procedures are capitalized on to propose an integrated set of improved methods to evaluate the efficacy of ASNase formulations against B\u2010cell ALL in mice, comprising the establishment of an ALL murine model not requiring humanization, an amino acid depletion study, and an assessment of antibody production. It is shown that unmodified ASNase results in short\u2010lived asparagine depletion and a strong immune response. PEG\u2010ASNase produces longer\u2010lasting asparagine depletion, reduces ALL cell counts, and minimizes anti\u2010ASNase immunogenicity but induces an increased immune response to PEG and is not curative without the chemotherapy backbone. With the increasing use of PEG\u2010modified drugs, these tools offer a framework for assessing pharmacokinetics and immunogenicity of new enzyme\u2010based therapeutics or nanoparticles.\n                  <\/jats:p>","DOI":"10.1002\/smtd.202500945","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T18:45:05Z","timestamp":1752518705000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Integrated Method to Evaluate the Treatment Efficacy and Immunogenicity of B\u2010Cell Acute Lymphoblastic Leukemia Therapeutic Enzyme Formulations"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-5831","authenticated-orcid":false,"given":"Julien","family":"Santelli","sequence":"first","affiliation":[{"name":"Department of Radiology Translational Research in Ultrasound Theranostics (TRUST) Program University of Texas Southwestern Medical Center  Dallas TX 75390 USA"},{"name":"Department of Biomedical Engineering University of Texas Southwestern Medical Center  Dallas TX 75390 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-5547","authenticated-orcid":false,"given":"Annie Y.","family":"Heble","sequence":"additional","affiliation":[{"name":"Department of Radiology Translational Research in Ultrasound Theranostics (TRUST) Program University of Texas Southwestern Medical Center  Dallas TX 75390 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Endsley","sequence":"additional","affiliation":[{"name":"Department of Radiology Translational Research in Ultrasound Theranostics (TRUST) Program University of Texas Southwestern Medical Center  Dallas TX 75390 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Woodward","sequence":"additional","affiliation":[{"name":"Department of Radiology Translational Research in Ultrasound Theranostics (TRUST) Program University of Texas Southwestern Medical Center  Dallas TX 75390 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia","family":"Hafeez","sequence":"additional","affiliation":[{"name":"Department of Radiology Translational Research in Ultrasound Theranostics (TRUST) Program University of Texas Southwestern Medical Center  Dallas TX 75390 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Winick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Texas Southwestern Medical Center  Dallas TX 75390 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7396-608X","authenticated-orcid":false,"given":"Jacques","family":"Lux","sequence":"additional","affiliation":[{"name":"Department of Radiology Translational Research in Ultrasound Theranostics (TRUST) Program University of Texas Southwestern Medical Center  Dallas TX 75390 USA"},{"name":"Department of Biomedical Engineering University of Texas Southwestern Medical Center  Dallas TX 75390 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"e_1_2_10_1_1","volume-title":"StatPearls","author":"Puckett Y.","year":"2023"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)33018-1"},{"key":"e_1_2_10_3_1","first-page":"5601","volume":"43","author":"Sallan S. 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