{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:09:39Z","timestamp":1791544179601,"version":"4.3.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T00:00:00Z","timestamp":1694822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Lumos Pharma, Inc."},{"DOI":"10.13039\/100001445","name":"Alex\u2019s Lemonade Stand Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cannonball Kids\u2019 cancer Foundation"},{"name":"Eli\u2019s Block Party Childhood Cancer Foundation"},{"name":"Hyundai Hope on Wheels Foundation"},{"name":"Miriam Lloyd Halsey Foundation"},{"name":"Northern Nevada Children\u2019s Cancer Foundation"},{"name":"Trial Blazers for Kids Foundation"},{"name":"Press On Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg\/m2\/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39\u201377 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg\/kg\/dose, twice daily. Median overall survival was 13.3 months (n\u2005=\u200568, range 0.2\u201362.7) for all patients with recurrent disease and 14.4 months (n\u2005=\u200513, range 4.7\u201329.7) for DIPG. The subset of n\u2005=\u200526 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4\u201361.9, p\u2005=\u20050.006) compared to n\u2005=\u200537 nonresponders (7.3 months, range 0.2\u201362.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II\/III trials for pediatric brain tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noad174","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T01:33:26Z","timestamp":1694655206000},"page":"348-361","source":"Crossref","is-referenced-by-count":51,"title":["Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial"],"prefix":"10.1093","volume":"26","author":[{"given":"Theodore S","family":"Johnson","sequence":"first","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"},{"name":"Department of Pediatrics, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobey J","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Aflac Cancer & Blood Disorders Center at Children\u2019s Healthcare of Atlanta and Department of Pediatrics, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Pacholczyk","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolly","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Aflac Cancer & Blood Disorders Center at Children\u2019s Healthcare of Atlanta and Department of Pediatrics, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Al-Basheer","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"},{"name":"Department of Radiation Oncology, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Bajaj","sequence":"additional","affiliation":[{"name":"Department of Radiology, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4175-4760","authenticated-orcid":false,"given":"Pratiti","family":"Bandopadhayay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Berrong","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6832-6539","authenticated-orcid":false,"given":"Eric","family":"Bouffet","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Hospital for Sick Children , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Castellino","sequence":"additional","affiliation":[{"name":"Aflac Cancer & Blood Disorders Center at Children\u2019s Healthcare of Atlanta and Department of Pediatrics, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0753-2176","authenticated-orcid":false,"given":"Kathleen","family":"Dorris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital Colorado , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bree R","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Winship Cancer Institute of Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natia","family":"Esiashvili","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Winship Cancer Institute of Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R","family":"Fangusaro","sequence":"additional","affiliation":[{"name":"Aflac Cancer & Blood Disorders Center at Children\u2019s Healthcare of Atlanta and Department of Pediatrics, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Foreman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital Colorado , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Fridlyand","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Giller","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M","family":"Heger","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenbin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University , Atlanta, Georgia , USA"},{"name":"Department of Biomedical Informatics, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Kadom","sequence":"additional","affiliation":[{"name":"Department of Radiology and Winship Cancer Institute of Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene P","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Lumos Pharma, Inc. (formerly NewLink Genetics Corporation) , Austin, Texas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neevika","family":"Manoharan","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"McDonough","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"},{"name":"Department of Pediatrics, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca S","family":"Parker","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"},{"name":"Department of Pediatrics, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6557-895X","authenticated-orcid":false,"given":"Vijay","family":"Ramaswamy","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Hospital for Sick Children , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Ring","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"},{"name":"Department of Pediatrics, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amyn","family":"Rojiani","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"},{"name":"Department of Pathology, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramses F","family":"Sadek","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University , Augusta, Georgia , USA"},{"name":"Department of Population Health Sciences, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarthak","family":"Satpathy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University , Atlanta, Georgia , USA"},{"name":"Department of Biomedical Informatics, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Schniederjan","sequence":"additional","affiliation":[{"name":"Children\u2019s Healthcare of Atlanta and Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Arnold Palmer Hospital for Children , Orlando, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Smith","sequence":"additional","affiliation":[{"name":"Lumos Pharma, Inc. (formerly NewLink Genetics Corporation) , Austin, Texas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beena E","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University , Atlanta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Vaizer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Augusta University , Augusta, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0713-6384","authenticated-orcid":false,"given":"Kee Kiat","family":"Yeo","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj K","family":"Bhasin","sequence":"additional","affiliation":[{"name":"Aflac Cancer & Blood Disorders Center at Children\u2019s 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