Cytotherapy最新文献

{"title":"Adipose-derived stem cell modulate tolerogenic dendritic cell-induced T cell regulation is correlated with activation of Notch-NFκB signaling","authors":"","doi":"10.1016/j.jcyt.2024.03.482","DOIUrl":"10.1016/j.jcyt.2024.03.482","url":null,"abstract":"<div><h3>Background</h3><p>Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs.</p></div><div><h3>Methods</h3><p>Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs.</p></div><div><h3>Results</h3><p>Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway).</p></div><div><h3>Conclusions</h3><p>ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924005747/pdfft?md5=a2236ae2ac1ca2dd629c1af2732f9d15&pid=1-s2.0-S1465324924005747-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140401546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex association of body mass index and outcomes in patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy","authors":"","doi":"10.1016/j.jcyt.2024.03.481","DOIUrl":"10.1016/j.jcyt.2024.03.481","url":null,"abstract":"<div><h3>Background aims</h3><p>Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy.</p></div><div><h3>Methods</h3><p>We conducted a retrospective study of 111 patients with R/R MM who underwent CAR-T cell treatment. Using the body mass index (BMI) classification, the patients were divided into a normal-weight group (73/111) and an overweight group (38/111). We investigated the effect of BMI on CAR-T cell therapy outcomes in patients with R/R MM.</p></div><div><h3>Results</h3><p>The objective remission rates after CAR-T cell infusion were 94.7% and 89.0% in the overweight and normal-weight groups, respectively. The duration of response and overall survival were not significant difference between BMI groups. Compared to normal-weight patients, overweight patients had an improved median progression-free survival. There was no significant difference in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome between the subgroups. In terms of hematological toxicity, the erythrocyte, hemoglobin, platelet, leukocyte and neutrophil recovery was accelerated in the overweight group. Fewer patients in the overweight group displayed moderate percent CD4 and CD4/CD8 ratios compared to the normal-weight group. Furthermore, the percent CD4 ratios were positively correlated with the levels of cytokines [interleukin-2 (IL-2) (day 14), interferon gamma (IFN-γ) (day 7) and tumor necrosis factor alpha (TNF-α) (days 14 and 21)] after cells infusion. On the other hand, BMI was positively associated with the levels of IFN-γ (day 7) and TNF-α (days 14 and 21) after CAR-T cells infusion.</p></div><div><h3>Conclusions</h3><p>Overall, this study highlights the potential beneficial effect of a higher BMI on CAR-T cell therapy outcomes.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400832","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}

{"title":"The evolving regulatory system of advanced therapy medicinal products in China: a documentary analysis using the World Health Organization Global Benchmarking Tool standards","authors":"","doi":"10.1016/j.jcyt.2024.04.070","DOIUrl":"10.1016/j.jcyt.2024.04.070","url":null,"abstract":"<div><p>Advanced therapy medicinal products (ATMPs) are rapidly evolving to offer new treatment options. The scientific, technical, and clinical complexities subject drug regulatory authorizes to regulatory challenges. To advance the regulatory capacity for ATMPs, the National Medical Products Administration in China made changes to the drug regulatory system and developed regulatory science with the goal of addressing patient needs and encouraging innovation. This study aimed to systematically identify the regulatory evidence on ATMPs in China under the guidance of an overarching framework from the World Health Organization Global Benchmarking Tool. It was found that China's administrative authorities at all levels have issued a number of policy documents to promote the development of ATMPs, covering biopharmaceutical products research and development (<em>n</em> = 14), biopharmaceutical industry development (<em>n</em> = 9), high-quality development of medical institutions (<em>n</em> = 1), specific development plans/projects (<em>n</em> = 6) and specific regional development (<em>n</em> = 4). The legal and regulatory framework of ATMPs in China has been established and is subject to continuous adjustment in various aspects including regulations (<em>n</em> = 3), departmental rules or administrative normative documents (<em>n</em> = 22), and technical guidance (<em>n</em> = 15). As the regulatory reform continues, the drug review processes have been revised, and various technical standards have been launched, which aim to establish a regulatory approach that oversees the full life-cycle development of ATMPs in the country. The limited number of investigational new drug applications and approved ATMPs suggests a lag remains between the translation of advanced therapeutic technologies into clinically available medical products. To accelerate the translational research of ATMP in countries such as China, developing and adopting real-world evidence generated from clinical use in designated healthcare facilities to support scientific decision-making in ATMP regulation is warranted. The enhancement of regulatory capacity building and multi-stakeholder collaborations should also be encouraged to facilitate the timely evaluation of promising ATMPs to meet more patient needs.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913337","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}

{"title":"Allogeneic transplantation of bone marrow versus peripheral blood stem cells from HLA-identical sibling donors for hematological malignancies in 6064 adults from 2003 to 2020: different impacts on survival according to time period","authors":"","doi":"10.1016/j.jcyt.2024.03.489","DOIUrl":"10.1016/j.jcyt.2024.03.489","url":null,"abstract":"<div><h3>Background</h3><p>Mobilized peripheral blood stem cells (PBSC) have been widely used instead of bone marrow (BM) as the graft source for allogeneic hematopoietic cell transplantation (HCT). Although early studies demonstrated no significant differences in survival between PBSC transplantation (PBSCT) and BM transplantation (BMT) from human leukocyte antigen (HLA)-identical sibling donors to adults with hematological malignancies, recent results have been unclear.</p></div><div><h3>Objective</h3><p>The objective of this retrospective study was to compare overall survival (OS), relapse, non-relapse mortality (NRM), hematopoietic recovery and graft-versus-host disease (GVHD) between PBSCT and BMT according to the time period of HCT (2003–2008, 2009–2014, or 2015–2020).</p></div><div><h3>Study design</h3><p>We retrospectively compared the outcomes after PBSCT versus BMT in 6064 adults with hematological malignancies using a Japanese registry database between 2003 and 2020.</p></div><div><h3>Results</h3><p>The adjusted probability of OS was significantly higher in BMT recipients compared to PBSCT recipients during the early period of 2003–2008 (adjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.70–0.91; <em>P</em> &lt; 0.001) and the middle period of 2009–2014 (adjusted HR, 0.80; 95% CI, 0.70–0.91; <em>P</em> &lt; 0.001). However, during the late period of 2015–2020, the adjusted probability of OS was comparable between BMT and PBSCT recipients (adjusted HR, 0.94; 95% CI, 0.79–1.13; <em>P</em> = 0.564), which were mainly due to the reduction of NRM. There was no significant difference in the relapse rate between the groups, irrespective of the time period. Compared to BMT, PBSCT led to faster neutrophil and platelet recovery and the cumulative incidences of grades II–IV and grades III–IV acute and overall and extensive chronic GVHD were significantly higher in PBSCT recipients, irrespective of the time period.</p></div><div><h3>Conclusions</h3><p>PBSCT and BMT had similar survival outcomes and relapse rates in adult patients with hematological malignancies during the late time period of 2015–2020 despite the hematopoietic recovery and acute and chronic GVHD being higher in PBSCT recipients in all time periods.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140407576","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}

{"title":"Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil","authors":"","doi":"10.1016/j.jcyt.2024.03.492","DOIUrl":"10.1016/j.jcyt.2024.03.492","url":null,"abstract":"<div><h3>Background aims</h3><p>The marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese), from a regulatory perspective.</p></div><div><h3>Methods</h3><p>A survey containing structured questions was conducted among research participants who work at companies that commercialize ATMPs. A descriptive analysis was performed.</p></div><div><h3>Results</h3><p>We invited 15 foreign pharmaceutical companies, of which 10 agreed to participate. Overall, participants assessed that Brazil has a well-established regulatory system, especially the sanitary registration by the National Health Surveillance Agency (Anvisa), which ensures the quality, safety, and efficacy of the products. The Agency's good interaction with the regulated sector, the harmonization of sanitary and ethical assessment systems with other countries, and the analysis time in the biosafety assessment of Genetically Modified Organisms (GMOs) stand out as positive in industry's evaluation. On the other hand, it is important to advance the pricing regulation for these products since Brazilian regulations do not establish specific criteria for ATMP. One of the biggest challenges is the difficulty for the SUS in reimbursing these very high-cost therapies, especially using current Health Technology Assessment (HTA) methods.</p></div><div><h3>Conclusions</h3><p>Considering the increasing number of approvals of cell and gene therapies in Brazil in the coming years, a close dialogue between the industry and the public sector is recommended to advance regulatory improvements (pricing and HTA). Additionally, the construction of policies to promote the national Health Economic-Industrial Complex, based on a mission-oriented vision that encourages innovative models of financing, especially those that consider risk-sharing and co-financing technologies, will help provide the population with universal, equitable and sustainable access to ATMP in the SUS.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403878","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}

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(24)00788-6","DOIUrl":"10.1016/S1465-3249(24)00788-6","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141960678","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}

{"title":"Functional single-cell analyses of mesenchymal stromal cell proliferation and differentiation using ALDH-activity and mitochondrial ROS content","authors":"","doi":"10.1016/j.jcyt.2024.04.003","DOIUrl":"10.1016/j.jcyt.2024.04.003","url":null,"abstract":"<div><h3>Baskground</h3><p>Previous research has unveiled a stem cell-like transcriptome enrichment in the aldehyde dehydrogenase-expressing (ALDH^high) mesenchymal stromal cell (MStroC) fraction. However, considering the heterogeneity of MStroCs, with only a fraction of them presenting bona fide stem cells (MSCs), the actual potency of ALDH as an MSC-specific selection marker remains an issue.</p></div><div><h3>Methods</h3><p>To address this, the proliferative and differentiation potential of individual ALDH^high and ALDH^low MStroCs incubated at low oxygen concentrations, estimated to mimic stem cell niches (0.1% O₂), were assayed using single-cell clonal analysis, compared to standard conditions (20% O₂).</p></div><div><h3>Results</h3><p>We confirm that a high proliferative capacity and multi-potent MSCs are enriched in the ALDH^high MStroC population, especially when cells are cultured at 0.1% O₂. Measurements of reduced/oxidized glutathione and mitochondrial superoxide anions with MitoSoX (MSX) indicate that this advantage induced by low oxygen is related to a decrease in the oxidative and reactive oxygen species (ROS) levels in the stem cell metabolic setup. However, ALDH expression is neither specific nor exclusive to MSCs, as high proliferative capacity and multi-potent cells were also found in the ALDH^low fraction. Furthermore, single-cell assays performed after combined cell sorting based on ALDH and MSX showed that the MSX^low MStroC population is enriched in stem/progenitor cells in all conditions, irrespective of ALDH expression or culture oxygen concentration. Importantly, the ALDH^highMSX^low MStroC fraction exposed to 0.1% O₂ was almost exclusively composed of genuine MSCs. In contrast, neither progenitors nor stem cells (with a complete absence of colony-forming ability) were detected in the MSX^high fraction, which exclusively resides in the ALDH^low MStroC population.</p></div><div><h3>Conclusion</h3><p>Our study reveals that ALDH expression is not exclusively associated with MSCs. However, cell sorting using combined ALDH expression and ROS content can be utilized to exclude MStroCs lacking stem/progenitor cell properties.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140768675","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}

{"title":"Ex-vivo expanded CD34+ cell transplantation alleviates fibrotic liver injury via innate immune modulation in metabolic dysfunction-associated steatohepatitis mice","authors":"","doi":"10.1016/j.jcyt.2024.03.488","DOIUrl":"10.1016/j.jcyt.2024.03.488","url":null,"abstract":"<div><h3>Background</h3><p>In drug-induced liver injury, vascular endothelial progenitor cells, specifically the CD34⁺ cell fractions, have been found to decrease liver fibrosis and promote regeneration. However, it is unclear whether CD34⁺ cell transplantation has anti-fibrogenic effects on MASH, which has previously been treated effectively with anti-angiogenic therapy. We investigated the efficacy of <em>ex vivo</em>-expanded CD34⁺ cells in treating MASH livers.</p></div><div><h3>Materials and methods</h3><p>Diet-induced MASH mice were fed a choline-deficient, L-amino acid-defined, high-fat diet for 12 or 20 weeks, and were designated as a mild and a severe fibrosis model, respectively. Mouse bone marrow CD34⁺ cells were expanded for 7 days, transplanted into each mouse once or twice 2 weeks later, and sacrificed at 4 weeks after the first transplantation.</p></div><div><h3>Results</h3><p>Expanded CD34⁺ cell transplantation ameliorated liver fibrosis, regardless of fibrosis degree, as indicated by the decrease in α-smooth muscle actin-positive cells, hydroxyproline concentration, and fibrogenic gene expression of <em>Col1a1</em> and <em>Timp1</em>. Furthermore, engrafted CD34⁺ cells reduced alanine transaminase levels, the number of TUNEL⁺ hepatocytes, and 8-OHdG concentration. RNA-sequencing data showed that \"defense response to virus\" was the most down-regulated category in the Gene Ontology analysis and subsequent analysis revealed the suppression of <em>RIG-I-like receptors/Irf7/Stat1/Cxcl10</em> axis in expanded CD34⁺ cell-transplanted livers. Finally, the downregulation of CXCL10 expression inhibits the mobilization of inflammatory immune cells, macrophages, T cells, and natural killer cells to the MASH liver.</p></div><div><h3>Conclusions</h3><p>These findings suggest that transplanted expanded CD34⁺ cells alleviate fibrotic liver injury in MASH mouse models through possible modulation of the innate immune response, which is abnormally activated by hepatocyte lipotoxicity.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140404260","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}

{"title":"Neutrophil generation from hematopoietic progenitor cells and induced pluripotent stem cells (iPSCs): potential applications","authors":"","doi":"10.1016/j.jcyt.2024.03.483","DOIUrl":"10.1016/j.jcyt.2024.03.483","url":null,"abstract":"<div><p>Neutrophils are the most frequent immune cell type in peripheral blood, performing an essential role against pathogens. People with neutrophil deficiencies are susceptible to deadly infections, highlighting the importance of generating these cells in host immunity. Neutrophils can be generated from hematopoietic progenitor cells (HPCs) and embryonic stem cells (ESCs) using a cocktail of cytokines. In addition, induced pluripotent stem cells (iPSCs) can be differentiated into various functional cell types, including neutrophils. iPSCs can be derived from differentiated cells, such as skin and blood cells, by reprogramming them to a pluripotent state. Neutrophil generation from iPSCs involves a multistep process that can be performed through feeder cell-dependent and feeder cell-independent manners. Various cytokines and growth factors, in particular, stem cell facto, IL-3, thrombopoietin and granulocyte colony-stimulating factor (G-CSF), are used in both methods, especially, G-CSF which induces the final differentiation of neutrophils in the granulocyte lineage. iPSC-derived neutrophils have been used as a valuable tool for studying rare genetic disorders affecting neutrophils. The iPSC-derived neutrophils can also be used for disease modeling, infection research and drug discovery. However, several challenges must be overcome before iPSC-derived neutrophils can be used therapeutically in transplantation medicine. This review provides an overview of the commonly employed protocols for generating neutrophils from HPCs, ESCs and iPSCs and discusses the potential applications of the generated cells in research and medicine.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140407138","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}

{"title":"Production of donor-derived cytotoxic T lymphocytes with potent anti-leukemia activity for adoptive immunotherapy in high-risk pediatric patients given haploidentical hematopoietic stem cell transplantation","authors":"","doi":"10.1016/j.jcyt.2024.04.005","DOIUrl":"10.1016/j.jcyt.2024.04.005","url":null,"abstract":"<div><h3>Background aims</h3><p>Somatic cell therapy based on the infusion of donor-derived cytotoxic T lymphocytes (CTL) able to recognize patients’ leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HSCT. The success of this approach strongly depends on the <em>ex vivo</em> generation of high-quality donor-derived anti-leukemia CTL in compliance with Good Manufacturing Practices (GMP). We previously described a procedure for generating large numbers of donor-derived anti-leukemia CTL through stimulation of CD8-enriched lymphocytes with dendritic cells (DCs) pulsed with apoptotic LB in the presence of interleukin (IL)-12, IL-7 and IL-15. Here we report that the use of IFN-DC and the addition of IFNα2b during the priming phase significantly improve the generation of an efficient anti-leukemia T cells response <em>in vitro</em>.</p></div><div><h3>Methods</h3><p>Using this approach, 20 high-risk pediatric patients given haploidentical HSCT for high-risk acute leukemia were enrolled and 51 batches of advanced therapy medical products (ATMP), anti-leukemia CTL, were produced.</p></div><div><h3>Results</h3><p>Quality controls demonstrated that all batches were sterile, free of mycoplasma and conformed to acceptable endotoxin levels. Genotype analysis confirmed the molecular identity of the ATMP based on the starting biological material used for their production. The majority of ATMP were CD3+/CD8+ cells, with a memory/terminal activated phenotype, including T-central memory populations. ATMP were viable after thawing, and most ATMP batches displayed efficient capacity to lyse patients’ LB and to secrete interferon-γ and tumor necrosis factor-α.</p></div><div><h3>Conclusions</h3><p>These results demonstrated that our protocol is highly reproducible and allows the generation of large numbers of immunologically safe and functional anti-leukemia CTL with a high level of standardization.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140768554","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}