{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:50:26Z","timestamp":1793058626093,"version":"4.5.0"},"reference-count":70,"publisher":"American Association for Cancer Research (AACR)","issue":"1","funder":[{"name":"National Cancer Institute","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that the genetic disruption of SUV39H1, which encodes a histone-3, lysine-9 methyl-transferase, enhances the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. Persisting SUV39H1-edited CAR T cells demonstrate improved expansion and tumor rejection upon multiple rechallenges. Transcriptional and genome accessibility profiling of repeatedly challenged CAR T cells shows improved expression and accessibility of memory transcription factors in SUV39H1-edited CAR T cells. SUV39H1 editing also reduces expression of inhibitory receptors and limits exhaustion in CAR T cells that have undergone multiple rechallenges. Our findings thus demonstrate the potential of epigenetic programming of CAR T cells to balance their function and persistence for improved adoptive cell therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>T cells engineered with CD28-based CARs possess robust effector function and antigen sensitivity but are hampered by limited persistence, which may result in tumor relapse. We report an epigenetic strategy involving disruption of the SUV39H1-mediated histone-silencing program that promotes the functional persistence of CD28-based CAR T cells.<\/jats:p>\n                    <jats:p>See related article by L\u00f3pez-Cobo et al., p. 120.<\/jats:p>\n                    <jats:p>This article is featured in Selected Articles from This Issue, p. 5<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-22-1319","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T09:08:24Z","timestamp":1699348104000},"page":"142-157","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Disruption of\n                    <i>SUV39H1<\/i>\n                    -Mediated H3K9 Methylation Sustains CAR T-cell Function"],"prefix":"10.1158","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9910-4824","authenticated-orcid":false,"given":"Nayan","family":"Jain","sequence":"first","affiliation":[{"name":"1Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-5033","authenticated-orcid":false,"given":"Zeguo","family":"Zhao","sequence":"additional","affiliation":[{"name":"2Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-5083","authenticated-orcid":false,"given":"Richard P.","family":"Koche","sequence":"additional","affiliation":[{"name":"3Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9610-7627","authenticated-orcid":false,"given":"Chenling","family":"Antelope","sequence":"additional","affiliation":[{"name":"4Immunai, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3816-3798","authenticated-orcid":false,"given":"Yosi","family":"Gozlan","sequence":"additional","affiliation":[{"name":"4Immunai, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7824-342X","authenticated-orcid":false,"given":"Antonino","family":"Montalbano","sequence":"additional","affiliation":[{"name":"4Immunai, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-8772","authenticated-orcid":false,"given":"David","family":"Brocks","sequence":"additional","affiliation":[{"name":"4Immunai, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5691-5272","authenticated-orcid":false,"given":"Michael","family":"Lopez","sequence":"additional","affiliation":[{"name":"2Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-0677","authenticated-orcid":false,"given":"Anton","family":"Dobrin","sequence":"additional","affiliation":[{"name":"1Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8483-0418","authenticated-orcid":false,"given":"Yuzhe","family":"Shi","sequence":"additional","affiliation":[{"name":"2Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2715-6980","authenticated-orcid":false,"given":"Gertrude","family":"Gunset","sequence":"additional","affiliation":[{"name":"2Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New 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