{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:13:25Z","timestamp":1791616405973,"version":"4.3.4"},"reference-count":36,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["10835"],"award-info":[{"award-number":["10835"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,6,7]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cellular immunotherapy using modified T cells offers new avenues for cancer treatment. T-cell receptor (TCR) engineering of CD8 T cells enables these cells to recognize tumor-associated antigens and tumor-specific neoantigens. Improving TCR T-cell therapy through increased potency and in vivo persistence will be critical for clinical success.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated a novel drug combination to enhance TCR therapy in mouse models for acute myeloid leukemia (AML) and multiple myeloma (MM).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Combining TCR therapy with the SUMO E1 inhibitor TAK981 and the DNA methylation inhibitor 5-Aza-2\u2019 deoxycytidine resulted in strong antitumor activity in a persistent manner against two in vivo tumor models of established AML and MM. We uncovered that the drug combination caused strong T-cell proliferation, increased cytokine signaling in T cells, improved persistence of T cells, and reduced differentiation towards exhausted phenotype. Simultaneously the drug combination enhanced immunogenicity of the tumor by increasing HLA and co-stimulation and surprisingly reducing inhibitory ligand expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Combining T-cell therapy with TAK981 and 5-Aza-2\u2019 deoxycytidine may be an important step towards improved clinical outcome.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-008654","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T05:15:13Z","timestamp":1727327713000},"page":"e008654","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting epigenetic regulation and post-translational modification with 5-Aza-2\u2019 deoxycytidine and SUMO E1 inhibition augments T-cell receptor therapy"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-6267","authenticated-orcid":false,"given":"Jessie S","family":"Kroonen","sequence":"first","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne K","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona J","family":"de Graaf","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis F G","family":"Remst","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-2530","authenticated-orcid":false,"given":"Tassilo L A","family":"Wachsmann","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina F A S","family":"Teunisse","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica P","family":"Roelands","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical 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