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Outcomes of tisagenlecleucel versus allogeneic hematopoietic stem cell transplantation in relapsed or refractory large B-cell lymphoma 复发或难治性大b细胞淋巴瘤的组织-白细胞与异体造血干细胞移植的结果
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-04-01 Epub Date: 2025-12-02 DOI: 10.1016/j.jcyt.2025.102028
Tong-Yoon Kim , Kyoung Il Min , Gi-June Min , Youngwoo Jeon , Seung-Ah Yahng , Seok-Goo Cho , Ki-Seong Eom
{"title":"Outcomes of tisagenlecleucel versus allogeneic hematopoietic stem cell transplantation in relapsed or refractory large B-cell lymphoma","authors":"Tong-Yoon Kim ,&nbsp;Kyoung Il Min ,&nbsp;Gi-June Min ,&nbsp;Youngwoo Jeon ,&nbsp;Seung-Ah Yahng ,&nbsp;Seok-Goo Cho ,&nbsp;Ki-Seong Eom","doi":"10.1016/j.jcyt.2025.102028","DOIUrl":"10.1016/j.jcyt.2025.102028","url":null,"abstract":"<div><h3>Background</h3><div>CD19-targeted chimeric antigen receptor (CAR)-T cell therapy has changed third-line treatment for relapsed/refractory large B-cell lymphoma (r/r LBCL). However, whether CAR-T therapy outperforms allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. The aim of this study was to compare the real-world outcomes of tisagenlecleucel (Tisa-cel) CAR-T therapy versus allo-HSCT in adults with r/r LBCL, with a focus on survival, relapse, and nonrelapse mortality (NRM).</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of adult patients treated with Tisa-cel (June 2022–October 2024) or allo-HSCT (April 2012–June 2023) at two Korean centers. Optimal cut-off points for continuous variables were determined using a survival-tree algorithm. Patient characteristics, overall survival (OS), progression-free survival (PFS), cumulative relapse, and NRM were compared between groups.</div></div><div><h3>Results</h3><div>In total, 127 patients were included (74 Tisa-cel, 53 allo-HSCT). Patients in the Tisa-cel group were older (median age of 61 versus 46 years) and had a higher proportion of high-risk disease than those in the allo-HSCT group. At 12 months, OS and PFS were similar between the two groups: OS was 50.1% and 45.3% with Tisa-cel and allo-HSCT (<em>P</em> = 0.784), respectively, and PFS was 40.8% and 35.9% (<em>P</em> = 0.819), respectively. NRM was significantly lower with Tisa-cel than with allo-HSCT (<em>P</em> = 0.009), although the cumulative incidence of relapse rates was similar (<em>P</em> = 0.066). Multivariable analysis identified poor response to bridging chemotherapy and refractory disease as predictors of inferior OS in both groups. An interval of less than 18 months from diagnosis to second relapse was independently associated with worse OS and PFS and a higher risk for relapse after allo-HSCT (<em>P</em> &lt; 0.001); nonetheless, it did not affect outcomes after Tisa-cel therapy. The median OS for patients experiencing a relapse within 18 months was 9.5 months with Tisa-cel and 4.7 months with allo-HSCT. The poorer survival in the allo-HSCT group was primarily influenced by excess NRM.</div></div><div><h3>Conclusions</h3><div>Tisa-cel provides disease control comparable to allo-HSCT while markedly reducing NRM, resulting in a clear survival advantage when relapse occurs within 18 months of diagnosis. These real-world data support the earlier use of CAR-T therapy in the treatment course for high-risk r/r LBCL.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 4","pages":"Article 102028"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Native amniotic fluid mesenchymal stem cell response in a model of fetal growth restriction 胎儿生长受限模型中的天然羊水间充质干细胞反应
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-04-01 Epub Date: 2025-12-27 DOI: 10.1016/j.jcyt.2025.102039
Abbie E. Naus , Kamila Moskowitzova , Ashlyn E. Whitlock , Ina Kycia , Tanya T. Dang , Shuqi B. Lin , Ranjan Maskey , David Zurakowski , Ronald Mathieu , Dario O. Fauza
{"title":"Native amniotic fluid mesenchymal stem cell response in a model of fetal growth restriction","authors":"Abbie E. Naus ,&nbsp;Kamila Moskowitzova ,&nbsp;Ashlyn E. Whitlock ,&nbsp;Ina Kycia ,&nbsp;Tanya T. Dang ,&nbsp;Shuqi B. Lin ,&nbsp;Ranjan Maskey ,&nbsp;David Zurakowski ,&nbsp;Ronald Mathieu ,&nbsp;Dario O. Fauza","doi":"10.1016/j.jcyt.2025.102039","DOIUrl":"10.1016/j.jcyt.2025.102039","url":null,"abstract":"<div><h3>Purpose</h3><div>We sought to determine the impact of fetal growth restriction (FGR) on the cellularity of the amniotic fluid, with a focus on its mesenchymal stem cell (MSC) population.</div></div><div><h3>Methods</h3><div>Four time-dated pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O2) cycles from gestational day 15 (E15) until term (E21; FGR group). Three time-dated pregnant Sprague-Dawley dams not exposed to hypoxia served as normal controls. At term, fresh amniotic fluid samples from all their fetuses (<em>n</em> = 88, equally divided between the two groups) underwent quantitative multicolor flow cytometry for the detection of live cells as well as of cells concomitantly expressing CD29, and CD44 (both are markers of MSCs), while being also negative for DAPI and CD45, utilizing standard gating strategies. Statistical analysis was by Wilcoxon rank-sum tests and median regression (<em>P</em> &lt; 0.05).</div></div><div><h3>Results</h3><div>Placental efficiency was significantly lower in the FGR group compared to controls (<em>P</em> &lt; 0.001), confirming reproduction of the disease model. There was no significant difference in the median individual amniotic fluid volume between the groups (<em>P</em> = 0.792). Compared to controls, FGR fetuses had statistically significantly lower densities of both total live cells as well as of live MSCs in the amniotic fluid (both <em>P</em> &lt; 0.001). There was a significant decrease in the total number of MSCs in the FGR group versus controls (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Native amniotic fluid MSC may be consumed in the setting of FGR. This provides further biological basis for transamniotic stem cell therapy as a potential novel treatment for this disease.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 4","pages":"Article 102039"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
International Society of Cell and Gene Therapy 2025 exosomes signature series: a thematic synthesis for advancing mesenchymal stromal cell-derived extracellular vesicle therapies 国际细胞和基因治疗学会2025外泌体签名系列:推进间充质基质细胞衍生的细胞外囊泡治疗的专题合成。
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-11-28 DOI: 10.1016/j.jcyt.2025.102016
Tobias Tertel , Bernd Giebel , Ryang Hwa Lee , Maurizio Muraca , Luis A. Ortiz , Ornella Parolini , Sylvain Perruche , Paul D. Robbins , Eva Rohde , Shannon R. Strader , Shuji Terai , Wei Seong Toh , Reza Yarani , Daniel J. Weiss , Elani F. Wiest , Sai Kiang Lim
{"title":"International Society of Cell and Gene Therapy 2025 exosomes signature series: a thematic synthesis for advancing mesenchymal stromal cell-derived extracellular vesicle therapies","authors":"Tobias Tertel ,&nbsp;Bernd Giebel ,&nbsp;Ryang Hwa Lee ,&nbsp;Maurizio Muraca ,&nbsp;Luis A. Ortiz ,&nbsp;Ornella Parolini ,&nbsp;Sylvain Perruche ,&nbsp;Paul D. Robbins ,&nbsp;Eva Rohde ,&nbsp;Shannon R. Strader ,&nbsp;Shuji Terai ,&nbsp;Wei Seong Toh ,&nbsp;Reza Yarani ,&nbsp;Daniel J. Weiss ,&nbsp;Elani F. Wiest ,&nbsp;Sai Kiang Lim","doi":"10.1016/j.jcyt.2025.102016","DOIUrl":"10.1016/j.jcyt.2025.102016","url":null,"abstract":"<div><div>At the International Society of Cell and Gene Therapy (ISCT) 2025 Annual Meeting in New Orleans, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) received unprecedented attention, reflecting their rapid shift from experimental concept to promising therapeutic candidates. Scientists, clinicians, industry leaders and regulators participated in focused sessions to examine the questions that will determine how, and when, these products can reach patients: What drives their therapeutic effects? How can manufacturing ensure consistent, clinically active preparations? What is required to gain regulatory confidence, and who will fund the journey? Four thematic threads emerged: (i) pinpointing the “active ingredient” in context-specific settings, (ii) aligning manufacturing with critical quality attributes and potency assays, (iii) engaging regulators as early as possible to align on mechanism-driven product definitions and (iv) ensuring sustainable funding, clear market positioning and trial designs that satisfy both regulatory and commercial requirements. This report summarizes these discussions into actionable priorities: define context-specific mechanisms, embed potency assays into early process development and manufacturing protocols, link analytics to clinical relevance and design development programs that unite scientific credibility with regulatory and market viability. The message from the ISCT 2025 Annual Meeting was clear: MSC-EV therapies are poised to progress from bench to bedside, but only if science, regulation and strategy advance together.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 102016"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Introducing quality by design approach in early process development to improve natural killer cell manufacturing robustness 在早期工艺开发中引入质量设计方法,以提高自然杀伤细胞制造的稳健性。
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-11-23 DOI: 10.1016/j.jcyt.2025.102011
Takuya Kikuchi, Ippei Takeuchi, Hideto Yamaguchi
{"title":"Introducing quality by design approach in early process development to improve natural killer cell manufacturing robustness","authors":"Takuya Kikuchi,&nbsp;Ippei Takeuchi,&nbsp;Hideto Yamaguchi","doi":"10.1016/j.jcyt.2025.102011","DOIUrl":"10.1016/j.jcyt.2025.102011","url":null,"abstract":"<div><div>Process development employing a quality by design (QbD) approach has been applied across various modalities and is also recommended for the development of cell-based therapeutics. Introducing QbD principles from the early stages of process development enables the establishment of manufacturing processes that are robust, high-yield and have a low risk of failure. The aim of this study was to develop a robust manufacturing process for natural killer (NK) cells by implementing a QbD strategy in the initial phase of process development. The QbD approach was applied to enhance NK cell proliferation and cytotoxic activity <em>in vitro</em>, with a particular focus on optimizing the parameters of the stimulation step. Using FMEA, five high-risk parameters were identified: coating duration, coating solution concentration, initial cell density, culture duration and cytokine concentration. Subsequent experimental investigations within a design of experiments framework were conducted to establish statistical models describing NK cell fold expansion and cytotoxicity. Contour profiles of the response surfaces were used to determine optimal parameter settings that satisfied cytotoxicity criterion while maximizing fold expansion. Monte Carlo simulations under these optimized conditions indicated a low probability of failing to meet the cytotoxicity criterion. This study demonstrates that QbD-based assessments can lead to robust manufacturing processes. Furthermore, our findings elucidate the relationships between process parameters, NK cell proliferation and cytotoxicity, contributing to improved quality and productivity in NK cell–based therapeutics.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 102011"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced antitumor efficacy of next-generation B7-H3 chimeric antigen receptor T cells containing CD28, CD137 and CD27 costimulatory domains in multiple myeloma 含有CD28、CD137和CD27共刺激结构域的下一代B7-H3嵌合抗原受体T细胞在多发性骨髓瘤中的抗肿瘤作用增强
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-11-26 DOI: 10.1016/j.jcyt.2025.102014
Krissada Natungnuy , Piriya Luangwattananun , Kamonlapat Supimon , Pornpimon Yuti , Punchita Rujirachaivej , Jatuporn Sujjitjoon , Mutita Junking , Seiji Okada , Pa-thai Yenchitsomanus
{"title":"Enhanced antitumor efficacy of next-generation B7-H3 chimeric antigen receptor T cells containing CD28, CD137 and CD27 costimulatory domains in multiple myeloma","authors":"Krissada Natungnuy ,&nbsp;Piriya Luangwattananun ,&nbsp;Kamonlapat Supimon ,&nbsp;Pornpimon Yuti ,&nbsp;Punchita Rujirachaivej ,&nbsp;Jatuporn Sujjitjoon ,&nbsp;Mutita Junking ,&nbsp;Seiji Okada ,&nbsp;Pa-thai Yenchitsomanus","doi":"10.1016/j.jcyt.2025.102014","DOIUrl":"10.1016/j.jcyt.2025.102014","url":null,"abstract":"<div><h3>Background</h3><div>Multiple myeloma (MM) remains an incurable disease despite significant advancements in treatment strategies. Chimeric antigen receptor (CAR) T cell therapies targeting B-cell maturation antigen have demonstrated clinical promise; however, their effectiveness is often limited by disease relapse, partly due to CAR T cell exhaustion. B7-homolog 3 (B7-H3), an immune checkpoint molecule that is overexpressed in MM and may suppress T cell function, represents a potential alternative target to improve CAR T cell efficacy and enhance disease control.</div></div><div><h3>Methods</h3><div>We engineered and characterized three generations of B7-H3-specific CAR T cells, second (B7H3.CAR2), third (B7H3.CAR3) and next-generation (B7H3.CAR-NG), each incorporating distinct costimulatory domains. B7H3.CAR2 contains the CD28 costimulatory domain, B7H3.CAR3 combines CD28 and CD137, and B7H3.CAR-NG incorporates CD28, CD137, and CD27 costimulatory modules. Their expression and function were evaluated <em>in vitro</em> using MM cell lines with differential B7-H3 expression. CAR T cell phenotype, cytotoxic activity, persistence and cytokine secretion were assessed through both short- and long-term coculture assays.</div></div><div><h3>Results</h3><div>B7-H3 expression levels varied across MM cell lines, with MM.1S exhibiting the highest and NCI-H929 the lowest expression. Second-, third- and next-generation B7-H3-specific CAR T cells (B7H3.CAR2, B7H3.CAR3, and B7H3.CAR-NG) were successfully generated, with CAR expression rates of 31.27 ± 8.63%, 29.90 ± 8.86% and 37.27 ± 8.69%, respectively. All three CAR T cell types selectively lysed B7-H3-positive MM.1S cells in an antigen density-dependent manner while sparing B7-H3-negative SupT1 cells. Among them, B7H3.CAR-NG T cells showed the highest cytotoxicity, lysing 53.22 ± 9.28% of MM.1S cells at a 1:1 effector-to-target ratio, compared to 11.66 ± 1.62% of SupT1 cells. In long-term cocultures, CAR-NG T cells demonstrated superior tumor control and persistence, likely due to a higher frequency of central memory T cells. Cytokine analysis revealed elevated secretion of effector molecules by CAR-NG T cells, indicating enhanced antitumor functionality.</div></div><div><h3>Conclusions</h3><div>B7-H3-specific CAR T cells exhibit potent antitumor activity against MM, with the next-generation construct (B7H3.CAR-NG) demonstrating superior cytotoxicity, persistence and cytokine production. These findings support the potential of B7H3.CAR-NG T cells as a promising therapeutic strategy for MM.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 102014"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ex vivo mesenchymal progenitor cell-based cord blood cell expansion and exofucosylation to enhance transplant engraftment 体外间充质祖细胞为基础的脐带血细胞扩增和外聚焦增强移植植入。
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-11-19 DOI: 10.1016/j.jcyt.2025.102010
Portia Smallbone , Mayela Mendt , Robert Sackstein , Mark R. Tanner , Indresh Kaur , Rafet Basar , Hind Rafei , May Daher , Bethany Overman , Gheath Al-Atrash , Amin M. Alousi , Qaiser Bashir , Chitra M. Hosing , Jin S. Im , Partow Kebriaei , Pinaki Banerjee , Keyur P. Patel , Jun Zou , Kai Cao , Issa Khouri , Amanda Olson
{"title":"Ex vivo mesenchymal progenitor cell-based cord blood cell expansion and exofucosylation to enhance transplant engraftment","authors":"Portia Smallbone ,&nbsp;Mayela Mendt ,&nbsp;Robert Sackstein ,&nbsp;Mark R. Tanner ,&nbsp;Indresh Kaur ,&nbsp;Rafet Basar ,&nbsp;Hind Rafei ,&nbsp;May Daher ,&nbsp;Bethany Overman ,&nbsp;Gheath Al-Atrash ,&nbsp;Amin M. Alousi ,&nbsp;Qaiser Bashir ,&nbsp;Chitra M. Hosing ,&nbsp;Jin S. Im ,&nbsp;Partow Kebriaei ,&nbsp;Pinaki Banerjee ,&nbsp;Keyur P. Patel ,&nbsp;Jun Zou ,&nbsp;Kai Cao ,&nbsp;Issa Khouri ,&nbsp;Amanda Olson","doi":"10.1016/j.jcyt.2025.102010","DOIUrl":"10.1016/j.jcyt.2025.102010","url":null,"abstract":"<div><div>Umbilical cord blood (CB) transplantion is limited by slower engraftment and higher failure rates compared to other allografts. We hypothesized that <em>ex vivo</em> expansion of CB using mesenchymal progenitor cells (MPCs) and exofucosylation to enforce expression of osteotropism-mediating sLeX would shorten engraftment time. Six patients with hematologic malignancies underwent transplantation with two CB units (CBUs). Five received one unmanipulated CBU and one MPC-expanded, exofucosylated CBU. Median neutrophil engraftment, platelets &gt;20,000/µL, and platelets &gt;50,000/µL were 29, 45, and 55 days, respectively. A sixth received one exofucosylated CBU and one MPC-expanded CBU, achieving neutrophil engraftment, platelets &gt;20,000/µL, and platelets &gt;50,000/µL in 34, 53, and 57 days, respectively. Acute GVHD occurred in 4/6 patients, including one grade III/IV case. Three were alive without disease relapse at a median of 43.6 months post-transplant. Deaths in three patients were due to relapse, COVID, and GVHD. Thus, these approaches were safe, but did not improve engraftment.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 102010"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Expanded adaptive NKG2C+ NK cells exhibit potent ADCC and functional responses against HBV-infected hepatoma cell lines 扩增的适应性NKG2C+ NK细胞对hbv感染的肝癌细胞系表现出有效的ADCC和功能性应答。
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-10-25 DOI: 10.1016/j.jcyt.2025.10.006
Jonida Kokiçi , Helena Arellano-Ballestero , Benjamin Hammond , Anucha Preechanukul , Noshin Hussain , Kelly da Costa , Jessica Davies , Sadiyah Mukhtar , Thomas Fernandez , Sabine Kinloch , Fiona M. Burns , Patrick Kennedy , Douglas MacDonald , Mala K. Maini , Upkar S. Gill , Alan Xiaodong Zhuang , Mark W. Lowdell , Karl-Johan Malmberg , Ebba Sohlberg , Dimitra Peppa
{"title":"Expanded adaptive NKG2C+ NK cells exhibit potent ADCC and functional responses against HBV-infected hepatoma cell lines","authors":"Jonida Kokiçi ,&nbsp;Helena Arellano-Ballestero ,&nbsp;Benjamin Hammond ,&nbsp;Anucha Preechanukul ,&nbsp;Noshin Hussain ,&nbsp;Kelly da Costa ,&nbsp;Jessica Davies ,&nbsp;Sadiyah Mukhtar ,&nbsp;Thomas Fernandez ,&nbsp;Sabine Kinloch ,&nbsp;Fiona M. Burns ,&nbsp;Patrick Kennedy ,&nbsp;Douglas MacDonald ,&nbsp;Mala K. Maini ,&nbsp;Upkar S. Gill ,&nbsp;Alan Xiaodong Zhuang ,&nbsp;Mark W. Lowdell ,&nbsp;Karl-Johan Malmberg ,&nbsp;Ebba Sohlberg ,&nbsp;Dimitra Peppa","doi":"10.1016/j.jcyt.2025.10.006","DOIUrl":"10.1016/j.jcyt.2025.10.006","url":null,"abstract":"<div><h3>Background</h3><div>Hepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic liver disease and hepatocellular carcinoma (HCC). Natural killer (NK) cells play an important role in the clearance of HBV-infected cells, but their efficacy is often compromised during chronic infection. Adaptive NK cells, characterized by NKG2C expression and enhanced functional responses, represent a promising therapeutic avenue for enhancing anti-HBV immunity and responses to HBV-driven cancers.</div></div><div><h3>Methods</h3><div>We applied an established protocol, involving K562-HLA-E expressing feeder cells and cytokines (IL-2), for the expansion of adaptive NK cells from cryopreserved T- and B cell depleted peripheral blood mononuclear cells (PBMCs) derived from donors with chronic HBV infection alone or with Human Immunodeficiency Virus (HIV) co-infection. We evaluated the adaptive profile of expanded NK cells, their antibody-dependent cellular cytotoxicity (ADCC) capacity and functional responses against hepatoma cell lines in the presence or absence of HBV infection.</div></div><div><h3>Results</h3><div>Expanded NK cells achieved &gt;97% purity, with the NKG2C positive population exhibiting a mean 100-fold expansion. These cells demonstrated a predominantly adaptive phenotype with high surface expression of NKG2C and cytotoxic potential (Granzyme B). They maintained high levels of CD16 surface expression and upregulated CD2, essential for ADCC. Functionally, expanded adaptive NK cells showed enhanced ADCC capacity and functional responses to K562 targets, naive, HBV integrant-expressing, and <em>de novo</em> infected hepatoma cell lines. TGF-β preconditioning induced tissue-resident features (CD103, CD49a) in expanded adaptive NK cells, while preserving their adaptive phenotype and functionality, enhancing their potential for liver targeted immunotherapy. Further, expanded adaptive NK cells demonstrated minimal reactivity against autologous activated T cells, suggesting limited off-target effects.</div></div><div><h3>Conclusions</h3><div>Our study demonstrates the first successful expansion of adaptive NK cells with robust functional responses from donors with chronic viral infection. This approach creates opportunities for NK cell-based therapies alone or in combination with monoclonal antibodies contributing to HBV functional cure strategies and the treatment of HBV-driven cancers.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 101996"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Outcomes following CD22 CAR T-cells in B-ALL: a tale of two manufacturing strategies CD22 CAR - t细胞治疗B-ALL的结果:两种制造策略的故事。
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-10-02 DOI: 10.1016/j.jcyt.2025.09.013
Alexandra Dreyzin , Anne Marijn Kramer , Bonnie Yates , Hao-Wei Wang , Bita Sahaf , Constance Yuan , Dorota Klysz , Ramya Tunuguntla , Zachary Ehlinger , Skyler Reitberg , Serifat Adebola , Angela Su , Risa Ebina-Shibuya , Dongya Jia , Sooraj Achar , Sunita Patil , Kathryn Martin , Nikeshan Jeyakumar , Kara L Davis , Terry Fry , Nirali N Shah
{"title":"Outcomes following CD22 CAR T-cells in B-ALL: a tale of two manufacturing strategies","authors":"Alexandra Dreyzin ,&nbsp;Anne Marijn Kramer ,&nbsp;Bonnie Yates ,&nbsp;Hao-Wei Wang ,&nbsp;Bita Sahaf ,&nbsp;Constance Yuan ,&nbsp;Dorota Klysz ,&nbsp;Ramya Tunuguntla ,&nbsp;Zachary Ehlinger ,&nbsp;Skyler Reitberg ,&nbsp;Serifat Adebola ,&nbsp;Angela Su ,&nbsp;Risa Ebina-Shibuya ,&nbsp;Dongya Jia ,&nbsp;Sooraj Achar ,&nbsp;Sunita Patil ,&nbsp;Kathryn Martin ,&nbsp;Nikeshan Jeyakumar ,&nbsp;Kara L Davis ,&nbsp;Terry Fry ,&nbsp;Nirali N Shah","doi":"10.1016/j.jcyt.2025.09.013","DOIUrl":"10.1016/j.jcyt.2025.09.013","url":null,"abstract":"<div><div>As use of chimeric antigen receptor (CAR) T-cells continues to grow, there is increasing interest in utilizing automated manufacturing systems as a mechanism to support decentralized manufacturing and increase access. However, most FDA approved CAR T-cell therapies are manufactured using traditional bag culture methodologies. Thus, understanding how different manufacturing platforms may impact outcomes is imperative. With parallel trials of CD22 CAR T-cells conducted in patients with B-cell acute lymphoblastic leukemia using a uniform vector but two different manufacturing strategies – either bag-culture (BC) or Prodigy – we were able to compare outcomes. Across 57 patients, 41 received BC cells and 16 received Prodigy-based cells. No significant differences in response rates or incidence of CAR-associated toxicities were observed between cohorts, although the BC cohort had slightly higher rates of severe CRS and IEC-HS. Peak ferritin and C-reactive protein levels were higher in the BC cohort. CAR T-cell expansion was similar, except for patients who had extramedullary disease with low bone marrow disease burden (n = 6 from each group), for whom BC-manufactured cells had greater expansion. In summary, while efficacy across both platforms was comparable, lower inflammatory markers in those who received Prodigy manufactured CAR T-cells suggest changes in the infusion product.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 101990"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to Synthetic receptor-based cell therapies for autoimmune diseases: an update Cytotherapy, Volume 27 (2025), P686-699 自身免疫性疾病合成受体细胞疗法的勘误表:更新细胞疗法,第27卷(2025),P686-699。
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-12-04 DOI: 10.1016/j.jcyt.2025.102013
Mieszko Lachota , Radosław Zagożdżon
{"title":"Corrigendum to Synthetic receptor-based cell therapies for autoimmune diseases: an update Cytotherapy, Volume 27 (2025), P686-699","authors":"Mieszko Lachota ,&nbsp;Radosław Zagożdżon","doi":"10.1016/j.jcyt.2025.102013","DOIUrl":"10.1016/j.jcyt.2025.102013","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 102013"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brain on the mend: induced mesenchymal stem cell−based therapies promote functional recovery in rats with neonatal hypoxic-ischemic brain injury 脑修复:诱导间充质干细胞治疗促进新生儿缺氧缺血性脑损伤大鼠功能恢复。
IF 3.2 3区 医学
Cytotherapy Pub Date : 2026-03-01 Epub Date: 2025-10-29 DOI: 10.1016/j.jcyt.2025.10.008
Inês Serrenho , Sofia C. Serra , António J. Salgado , Graça Baltazar
{"title":"Brain on the mend: induced mesenchymal stem cell−based therapies promote functional recovery in rats with neonatal hypoxic-ischemic brain injury","authors":"Inês Serrenho ,&nbsp;Sofia C. Serra ,&nbsp;António J. Salgado ,&nbsp;Graça Baltazar","doi":"10.1016/j.jcyt.2025.10.008","DOIUrl":"10.1016/j.jcyt.2025.10.008","url":null,"abstract":"<div><h3>Background aims</h3><div>Neonatal hypoxic-ischemic encephalopathy (HIE) remains a leading cause of infant mortality and long-term neurologic disability. Although therapeutic hypothermia (TH) is the current standard treatment, its effectiveness is limited, with many infants either ineligible or showing incomplete recovery. As a result, alternative therapies, such as mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iMSCs), are being explored. iMSCs have shown considerable promise in preclinical studies because of their consistent properties, which help overcome some of the challenges associated with traditional MSCs. This study evaluated the efficacy of iMSCs and their secretome in promoting recovery after neonatal hypoxic-ischemic (HI) brain injury in a well-established rodent model.</div></div><div><h3>Methods</h3><div>The Rice-Vannucci model was used to induce HI brain injury to the developing brain on postnatal day 10 (P10) Wistar Han rat pups. Two days post-injury, 50 000 iMSCs or their secretome were administered intranasally. Over the next 30 days, motor and cognitive functions were assessed through a series of behavioral tests. In addition, brain lesion size, neurogenesis and glial reactivity were examined by immunohistochemistry to evaluate the extent of neurorepair and inflammation.</div></div><div><h3>Results</h3><div>HI-lesioned animals treated with intranasal iMSCs or their secretome demonstrated improved motor capabilities and enhanced recognition memory compared with untreated lesioned animals. Both iMSCs and their secretome administration led to a reduction in brain lesion size and increased neurogenesis in the hippocampus. Moreover, glial reactivity, including astrocyte and microglia activation, was significantly reduced 30 days after injury, suggesting a more favorable neuroinflammatory environment in treated groups.</div></div><div><h3>Conclusions</h3><div>These findings highlight the potential of iMSCs and their secretome to enhance functional recovery and reduce brain damage after neonatal HI. The similar therapeutic outcomes achieved with the iMSC secretome suggest that the secreted factors play a central role in driving neurorepair. More studies are still necessary to gain a better understanding of the mechanisms underlying iMSCs' neuroprotective and neuroreparative effects.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"28 3","pages":"Article 101998"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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