{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:34:57Z","timestamp":1792121697712,"version":"4.4.0"},"reference-count":42,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,25]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>For patients with high-risk or relapsed\/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. However, the concurrent transfer of alloreactive T cells can lead to graft-versus-host disease that is associated with transplant-related morbidity and mortality. Furthermore, \u223c60% of patients will ultimately relapse after allo-HSCT, thus, underscoring the need for novel therapeutic strategies that are safe and effective. In this study, we explored the feasibility of immunotherapeutically targeting neoantigens, which arise from recurrent nonsynonymous mutations in AML and thus represent attractive targets because they are exclusively present on the tumor. Focusing on 14 recurrent driver mutations across 8 genes found in AML, we investigated their immunogenicity in 23 individuals with diverse HLA profiles. We demonstrate the immunogenicity of AML neoantigens, with 17 of 23 (74%) reactive donors screened mounting a response. The most immunodominant neoantigens were IDH2R140Q (n\u00a0= 11 of 17 responders), IDH1R132H (n\u00a0= 7 of 17), and FLT3D835Y (n\u00a0= 6 of 17). In-depth studies of IDH2R140Q-specific T cells revealed the presence of reactive CD4+ and CD8+ T\u00a0cells capable of recognizing distinct mutant-specific epitopes restricted to different HLA alleles. These neo\u2013T cells could selectively recognize and kill HLA-matched AML targets endogenously expressing IDH2R140Q both in\u00a0vitro and in\u00a0vivo. Overall, our findings support the clinical translation of neoantigen\u2013specific T cells to treat relapsed\/refractory AML.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023021979","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T21:11:17Z","timestamp":1705698677000},"page":"1726-1737","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":18,"title":["Targeting IDH2R140Q and other neoantigens in acute myeloid leukemia"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2252-5217","authenticated-orcid":false,"given":"Wingchi K.","family":"Leung","sequence":"first","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children\u2019s Hospital, and Houston Methodist Hospital, Houston, 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