{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:25:25Z","timestamp":1790130325409,"version":"4.0.1"},"reference-count":138,"publisher":"American Association for Cancer Research (AACR)","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5K08CA263179"],"award-info":[{"award-number":["5K08CA263179"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015151","name":"Stand Up To Cancer Canada","doi-asserted-by":"publisher","award":["SU2C-AACR-DT-27-17"],"award-info":[{"award-number":["SU2C-AACR-DT-27-17"]}],"id":[{"id":"10.13039\/100015151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Central nervous system (CNS) tumors are a leading cause of pediatric cancer-related death. Chimeric antigen receptor (CAR) T cells are an innovative approach for these affected children who are in desperate need of novel therapies, but CNS-directed cellular therapies have only recently advanced to the clinic. Although early-phase trials have begun to demonstrate the feasibility of manufacturing fractionated doses and the tolerability of repeated infusions for children with CNS tumors, major challenges remain. In this review, we will take an inventory of the current state of the pediatric CNS CAR T-cell field through the lens of translational obstacles to broader clinical success.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>CNS tumors are the leading cause of cancer-related death in children, highlighting the dire need for new treatment strategies. CAR T cells represent a unique approach, distinct from the cytotoxic chemotherapies and small-molecule inhibitors that have dominated the clinical trial space for decades. Phase I CAR T-cell trials have shown feasibility and possible efficacy against pediatric CNS tumors; however, many challenges must be overcome if these therapeutics are going to be beneficial to most affected children. Although rapid translational development and early-phase trials have quickly evolved our understanding, the pediatric CNS CAR T-cell community now yearns for critical assessments and open dialogue about overcoming the remaining obstacles ahead.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-24-1465","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T15:31:58Z","timestamp":1745940718000},"page":"890-902","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Evolving CAR T-Cell Therapy to Overcome the Barriers in Treating Pediatric Central Nervous System Tumors"],"prefix":"10.1158","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3955-3481","authenticated-orcid":false,"given":"Andrea","family":"Timpanaro","sequence":"first","affiliation":[{"name":"1Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4022-9753","authenticated-orcid":false,"given":"Edward Z.","family":"Song","sequence":"additional","affiliation":[{"name":"1Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0842-9640","authenticated-orcid":false,"given":"Nour","family":"Amwas","sequence":"additional","affiliation":[{"name":"2Department of Immuno-oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0570-2465","authenticated-orcid":false,"given":"Chu-Hsuan","family":"Chiu","sequence":"additional","affiliation":[{"name":"2Department of Immuno-oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3961-3042","authenticated-orcid":false,"given":"Rebecca","family":"Ronsley","sequence":"additional","affiliation":[{"name":"1Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute, Seattle, Washington."},{"name":"3Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8998-4530","authenticated-orcid":false,"given":"Mallory R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"1Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute, Seattle, Washington."},{"name":"3Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8001-5960","authenticated-orcid":false,"given":"Jessica B.","family":"Foster","sequence":"additional","affiliation":[{"name":"4Division of Oncology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania."},{"name":"5Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-9005","authenticated-orcid":false,"given":"Leo D.","family":"Wang","sequence":"additional","affiliation":[{"name":"2Department of Immuno-oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California."},{"name":"6Department of Pediatrics, City of Hope Children\u2019s Cancer Center, Duarte, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3966-4985","authenticated-orcid":false,"given":"Nicholas A.","family":"Vitanza","sequence":"additional","affiliation":[{"name":"1Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute, Seattle, Washington."},{"name":"3Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington, Seattle, Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"2026041510365286100_bib1","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1182\/blood-2017-02-769208","article-title":"Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young 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