{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:36:24Z","timestamp":1790620584225,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"ChadTough Defeat DIPG Foundation"},{"DOI":"10.13039\/100005410","name":"American-Italian Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001906","name":"Washington Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001906","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Invent at Seattle Children\u2019s Postdoctoral Scholars Program"},{"name":"Yuvaan Tiwari Foundation"},{"name":"DIPG\/DMG Research Funding Alliance"},{"name":"Cancer Dream Team Translational Cancer Research Grants","award":["SU2C-AACR-DT-27-17"],"award-info":[{"award-number":["SU2C-AACR-DT-27-17"]}]},{"name":"National Cancer Institute of the National Institutes of Health","award":["R37CA289981; N.A.V"],"award-info":[{"award-number":["R37CA289981; N.A.V"]}]},{"name":"Avery Huffman DIPG Foundation"},{"name":"Ezra Blue\u2019s Flight for Cancer"},{"name":"Live Like a Unicorn, Live Gray\u2019s Way, Love for Lucy, the McKenna Claire Foundation"},{"name":"Pediatric Brain Tumor Research Fund Guild of Seattle Children\u2019s"},{"name":"Team Cozzi Foundation, and Unravel Pediatric Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor affecting over 300 children annually in the United States. Chimeric antigen receptor (CAR) T cells are a targeted immune effector cell therapy with substantial clinical benefit against hematologic cancers. Against central nervous system (CNS) tumors, CAR T cells targeting B7-H3, a protein highly expressed on DIPG, have rapidly advanced from preclinical studies to clinical trials. BrainChild-03 (NCT04185038), a phase 1 trial of repeatedly delivered intracerebroventricular (ICV) B7-H3-targeting CAR T cells (B7-H3 CAR T cells), demonstrated tolerability and potential efficacy for children and young adults with DIPG. However, clinical benefits were not uniformly seen, and multi-agent treatment strategies may be required against such an aggressive disease. Here, we combined B7-H3 CAR T cells with ONC206, an imipridone molecule also under clinical investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested B7-H3 CAR T cells combined with ONC206 across multiple DIPG cell cultures and orthotopic xenograft mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>B7-H3 CAR T cell monotherapy induced robust cytotoxicity while ONC206 treatment resulted in significant mitochondrial dysfunction against DIPG cells. The combination of low effector-to-target ratios of B7-H3 CAR T cells and IC50 concentrations of ONC206 led to significantly enhanced cytotoxicity in vitro (P\u2009&amp;lt;\u2009.003) and increased IL-2, IL-29, VEGF-A, and Granzyme B levels. In vivo combinatorial studies of ONC206 and a single ICV dose of B7-H3 CAR T cells extended survival in DIPG xenograft mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>B7-H3 CAR T cells combined with ONC206 are a feasible and efficacious multi-agent approach against multiple DIPG models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag025","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T12:45:33Z","timestamp":1769777133000},"page":"1301-1315","source":"Crossref","is-referenced-by-count":3,"title":["Preclinical efficacy of combinatorial B7-H3 CAR T cells and ONC206 against diffuse intrinsic pontine glioma"],"prefix":"10.1093","volume":"28","author":[{"given":"Andrea","family":"Timpanaro","sequence":"first","affiliation":[{"name":"Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute , Seattle, Washington (A.T., E.Z.S., R.T., L.E.-S., K.M.N., A.K., D.L., S.J., L.W., A.R., R.R., S.K.O., M.E., S.P., M.M., M.C.B., N.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward Z","family":"Song","sequence":"additional","affiliation":[{"name":"Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute , Seattle, Washington (A.T., E.Z.S., R.T., L.E.-S., K.M.N., A.K., D.L., S.J., L.W., A.R., R.R., S.K.O., M.E., S.P., M.M., M.C.B., N.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryma","family":"Toumi","sequence":"additional","affiliation":[{"name":"Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute , Seattle, Washington (A.T., E.Z.S., R.T., L.E.-S., K.M.N., A.K., D.L., S.J., L.W., A.R., R.R., S.K.O., M.E., S.P., M.M., M.C.B., 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Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute , Seattle, Washington (A.T., E.Z.S., R.T., L.E.-S., K.M.N., A.K., D.L., S.J., L.W., A.R., R.R., S.K.O., M.E., S.P., M.M., M.C.B., N.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Winter","sequence":"additional","affiliation":[{"name":"Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute , Seattle, Washington (A.T., E.Z.S., R.T., L.E.-S., K.M.N., A.K., D.L., S.J., L.W., A.R., R.R., S.K.O., M.E., S.P., M.M., M.C.B., N.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashmitha","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children\u2019s Research Institute , Seattle, Washington (A.T., E.Z.S., R.T., L.E.-S., K.M.N., A.K., D.L., S.J., L.W., A.R., R.R., S.K.O., M.E., S.P., M.M., M.C.B., 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Seattle Children\u2019s Research Institute , Seattle, Washington (A.T., E.Z.S., R.T., L.E.-S., K.M.N., A.K., D.L., S.J., L.W., A.R., R.R., S.K.O., M.E., S.P., M.M., M.C.B., N.A.V.)"},{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington (R.R., S.K.O., M.E., S.P., N.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A","family":"Gustafson","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Therapeutics , Seattle, Washington (R.R., J.A.G., J.P.W., M.C.J., N.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P","family":"Wendler","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Therapeutics , Seattle, Washington (R.R., J.A.G., J.P.W., M.C.J., N.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Koschmann","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, 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