{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:30:27Z","timestamp":1781332227662,"version":"3.54.1"},"reference-count":37,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed\/refractory (r\/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r\/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r\/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r\/r DLBCL (N = 115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon-\u03b3 in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r\/r B-ALL and 94% of patients with r\/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r\/r B-ALL and 9% of r\/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics, including maximum concentration and persistence (r2 &amp;lt; 0.05), clinical response (day-28 response, duration of response, and event-free survival), and safety. T-cell responses were consistent over time, with net responses &amp;lt;1% at baseline and posttreatment time points in a majority of patients and no effect on transgene expansion or persistence or outcomes. Presence of baseline and\/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenlecleucel in patients with r\/r B-ALL or r\/r DLBCL.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003844","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T19:57:34Z","timestamp":1629921454000},"page":"4980-4991","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":26,"title":["Tisagenlecleucel immunogenicity in relapsed\/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma"],"prefix":"10.1182","volume":"5","author":[{"given":"Karen","family":"Thudium Mueller","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research, East Hanover, NJ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan A.","family":"Grupp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"},{"name":"Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon L.","family":"Maude","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"},{"name":"Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-7828","authenticated-orcid":false,"given":"John E.","family":"Levine","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, MI;"},{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-8420","authenticated-orcid":false,"given":"Michael A.","family":"Pulsipher","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children\u2019s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Internal Medicine, University of Utah, Salt Lake City, UT;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-0855","authenticated-orcid":false,"given":"Keith J.","family":"August","sequence":"additional","affiliation":[{"name":"Children\u2019s Mercy Hospital, Kansas City, MO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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