Blood immunology & cellular therapy.最新文献

{"title":"Lipid Nanoparticle Fas Gene Therapy Suppresses Autoimmune Lymphoproliferative Syndrome in Mice.","authors":"Dakota B Poschel, Zainab Tiamiyu, Priscilla Redd, Alyssa Merting, Natasha Savage, Kebin Liu","doi":"10.1016/j.bict.2025.100010","DOIUrl":"10.1016/j.bict.2025.100010","url":null,"abstract":"<p><p>Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disease of deregulated leukocyte homeostasis caused by <i>FAS</i> gene mutation or loss of Fas function. Despite three decades having passed since its discovery, except for bone marrow stem transplantation, there is currently no effective treatment for ALPS. The recent breakthrough of COVID-19 mRNA vaccine demonstrated the effectiveness of nucleic acid-based therapy for a human disease. We determined that Fas mediates caspase activation-dependent apoptosis of human hematopoietic cells in vitro. In the ALPS mice, loss of Fas function leads to decreased hematopoietic cell spontaneous apoptosis and mass accumulation of lymphocytes. To restore Fas expression and function, we generated lipid nanoparticle-encapsulated Fas-encoding plasmid (LNP-mFas). LNP-mFas therapy decreased the accumulation of CD4^-CD8^- lymphocytes and increased CD4⁺ and CD8⁺ mature T cells in mice, resulting in suppression of ALPS in mice. We therefore determine that LNP-mFas is potentially an effective therapy for ALPS.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"1 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12890007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late effects following CAR T cells and HCT in children and young adults with B-cell acute lymphoblastic leukemia.","authors":"Bonnie Yates, Chloe N Hoang, Flavia Gava, Victoria M Giordani, Lauren Little, Monica Epstein, Jillian Brems, Casey McGrath, Toni Foley, Haneen Shalabi, Nirali N Shah","doi":"10.1016/j.bict.2025.100008","DOIUrl":"10.1016/j.bict.2025.100008","url":null,"abstract":"","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining antigen specific T-cells with T-cell engager therapy induces a molecular signature that favors T-cell fitness.","authors":"Manpreet Bariana, Sidharth Anand, Mark Batistick, Elena Cassella, Shaina A Anuncio, Ariel Aptekmann, David S Siegel, Mathias Oelke, Sojung Kim, Ruipeng Wang, Jack A Ragheb, Johannes L Zakrzewski","doi":"10.1016/j.bict.2025.100002","DOIUrl":"10.1016/j.bict.2025.100002","url":null,"abstract":"<p><p>Both adoptive cellular therapy with tumor antigen-specific T-cells and redirection of endogenous T-cells with bispecific tumor-specific T-cell engaging antibodies rely on CD8⁺ T-cell effector function. The two approaches employ complementary mechanisms of action (T-cell receptor (TCR)/MHC dependent vs independent tumor cell killing), making them ideal candidates for combinatorial strategies. TCR and T-cell engager (TCE) mediated killing of tumor cells was determined by luciferase assay. T-cell phenotypes were analyzed by multiparameter flow cytometry. NFAT transcriptional activity was measured by Jurkat NFAT luciferase reporter cell assay. Transcriptional changes in antigen-specific T-cells isolated from the bone marrow of THP-1 bearing NSG MHC I/II double knockout mice were analyzed by bulk RNA-seq and pathway analysis was performed by gene set enrichment analysis (GSEA). Compared with the pool of naturally occurring polyclonal (bulk) CD8⁺ T-cells, <i>ex vivo</i> primed and expanded antigen-specific T-cells possess an enhanced capacity to mediate TCE efficacy. Both <i>in vitro</i> and <i>ex vivo</i> analyses confirmed that reduced T-cell activation-induced loss of CD3 correlated with TCE treatment of antigen-specific T-cells, suggesting that CD3 could serve as a surrogate biomarker for TCE activity in this context. TCE treatment of antigen-specific T-cells was associated with reduced NFAT transcriptional activity and decreased PD-1 expression while expression of the transcription factor TCF1 was increased, consistent with a molecular signature favoring CD8⁺ T-cell fate decisions leading to a less exhausted phenotype. In summary, the integration of antigen-specific T-cell and TCE therapies presents an attractive opportunity for combinatorial cancer immunotherapy, and it induces a molecular signature preserving T-cell fitness.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive profiling of AML and T-cell states across disease stages in acute myeloid leukemia using spectral flow cytometry.","authors":"Mhd Yousuf Yassouf, Jessica L Root, Poonam N Desai, Nicole R Vaughn, Ferdinandos Skoulidis, Hussein A Abbas, Patrick K Reville","doi":"10.1016/j.bict.2025.100004","DOIUrl":"10.1016/j.bict.2025.100004","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by clonal expansion of myeloid precursors, yet the interplay between leukemic and immune cells across disease stages remains poorly understood. Here, we used spectral flow cytometry and high-dimensional computational analyses to profile peripheral blood mononuclear cells from 72 patients with AML across 3 disease stages: newly diagnosed, remission, and relapsed/refractory. Clustering analyses identified stage-specific enrichment patterns in myeloid and lymphoid populations, with leukemic CD34⁺ and CD123⁺ cells dominating in relapsed/refractory patients and monocytic and CD45^low clusters enriched in remission. T-cell profiling revealed terminal effector and senescent subsets in relapsed/refractory patients, suggesting immune exhaustion as a contributor to disease progression. Mutation-specific analyses linked <i>TP53</i>, <i>DNMT3A</i>, and <i>NPM1</i> mutations to distinct enrichment patterns in both leukemic and immune populations, including increased CD71⁺ AML cells and altered T-cell distributions. These findings provide insights into the dynamic cellular ecosystem of AML, highlighting mutation-driven immune dysregulation and potential therapeutic targets to improve outcomes. This comprehensive profiling underscores the critical role of immune modulation in AML progression and relapse, paving the way for novel immune-targeted therapies.</p>","PeriodicalId":520924,"journal":{"name":"Blood immunology & cellular therapy.","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}