Cytotherapy最新文献

{"title":"CD19-chimeric antigen receptor-invariant natural killer T cells transactivate NK cells and reduce alloreactivity","authors":"Anton Wesle ,&nbsp;Emmanuelle Moraes Ribeiro ,&nbsp;Rebekka Schairer ,&nbsp;Hildegard Keppeler ,&nbsp;Fulya Korkmaz ,&nbsp;Pia Radszuweit ,&nbsp;Kristin Bieber ,&nbsp;Claudia Lengerke ,&nbsp;Dominik Schneidawind ,&nbsp;Corina Schneidawind","doi":"10.1016/j.jcyt.2024.08.004","DOIUrl":"10.1016/j.jcyt.2024.08.004","url":null,"abstract":"<div><div>Invariant natural killer T (iNKT) cells are a small fraction of T lymphocytes with strong cytotoxic and immunoregulatory properties. We previously showed that human culture-expanded iNKT cells prevent alloreactivity and lyse primary leukemia blasts. Here, iNKT cells have several advantages over T cells based on their immunoregulatory capabilities. Since chimeric antigen receptors (CARs) increase the benefit of immune effector cells, they play a crucial role in improvement of cytotoxic abilities of novel cellular therapeutics such as iNKT cells. In the present study, we investigated transactivation of NK cells and prevention of alloreactivity through iNKT cells transduced with a CD19-directed CAR. iNKT cells were isolated by magnetic cell separation from peripheral blood mononuclear cells and transduced with a CD19-CAR retrovirus. Transduction efficiency, purity and cell subsets were measured by flow cytometry. Transactivation and cytotoxicity assays have been established to investigate the ability of CD19-CAR-iNKT cells to transactivate primary NK cells. A mixed lymphocyte reaction (MLR) was performed to explore the inhibition of alloreactive CD3+ T cells by CD19-CAR-iNKT cells. CD19-CAR-iNKT cells are able to transactivate NK cells independent of cell contact: The expression of activation marker CD69 was significantly increased and also production of the proinflammatory cytokine interferon-gamma was higher in NK cells pretreated with CD19-CAR-iNKT cells. Consequently, the cytotoxic activity of such NK cells was significantly increased being able to lyse leukemia cells more effectively than without prior transactivation. Adding CD19-CAR-iNKT cells to an MLR resulted in a decreased expression of the T cell activation marker CD25 on alloreactive CD3+ T lymphocytes stimulated with HLA mismatched dendritic cells. Also, the proliferation of alloreactive CD3+ T lymphocytes was significantly reduced in this setting. We demonstrate that CD19-CAR-iNKT cells keep their immunoregulatory properties despite transduction with a CAR making them an attractive effector cell population for application after allogeneic hematopoietic cell transplantation. By transactivating NK cells, increasing their cytotoxic activity and suppressing alloreactive T cells, they might further improve outcomes through prevention of both relapse and graft-versus-host disease.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Pages 7-15"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248123","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":"The role of the conditioning regimen for autologous and ex vivo genetically modified hematopoietic stem cell-based therapies: recommendations from the ISCT stem cell engineering committee","authors":"Joseph H. Oved ,&nbsp;Athena Russell ,&nbsp;Amy DeZern ,&nbsp;Susan E Prockop ,&nbsp;Carmem Bonfim ,&nbsp;Akshay Sharma ,&nbsp;Duncan Purtill ,&nbsp;Madhavi Lakkaraja ,&nbsp;Alan Bidgoli ,&nbsp;Senthil Velan Bhoopalan ,&nbsp;Sandeep Soni ,&nbsp;Jaap Jan Boelens ,&nbsp;Allistair Abraham","doi":"10.1016/j.jcyt.2024.09.001","DOIUrl":"10.1016/j.jcyt.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><div>The advent of autologous gene modified cell therapies to treat monogenic disorders has been a major step forward for the field of hematopoietic stem cell transplantation (HCT) and cellular therapies. The need for disease-specific conditioning to enable these products to provide a potential cure has required extrapolation from experience in myeloablative and non-myeloablative HCT for these disorders.</div></div><div><h3>Methods</h3><div>In this manuscript, we review the current datasets and clinical experience using different conditioning regimens for autologous gene therapies in hemoglobinopathies, metabolic and lysosomal disorders, inborn errors of immunity (IEI) and bone marrow failure (BMF) syndromes.</div></div><div><h3>Results</h3><div>The disease specific and unique conditioning requirements of each disorder are considered in order to achieve maximal benefit while minimizing associated toxicities.</div></div><div><h3>Conclusions</h3><div>Standardized recommendations based on these data are made for each set of disorders to harmonize treatment. Future directions and the possibility of non-genotoxic conditioning regimens for autologous gene therapies are also discussed. Ethical Statement: The authors followed all relevant ethical considerations in writing this manuscript.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Pages 78-84"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331707","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":"Corrigendum to Real-time semantic segmentation and anomaly detection of functional images for cell therapy manufacturing Cytotherapy 25 (2023) 1361 - 1369","authors":"Rui Qi Chen ,&nbsp;Benjamin Joffe ,&nbsp;Paloma Casteleiro Costa ,&nbsp;Caroline Serafini ,&nbsp;Bryan Wang ,&nbsp;Stephen Balakirsky ,&nbsp;Francisco Robles ,&nbsp;Krishnendu Roy ,&nbsp;Jing Li","doi":"10.1016/j.jcyt.2024.11.010","DOIUrl":"10.1016/j.jcyt.2024.11.010","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Page 135"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710850","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":"Bioreactor on a chip: a microfluidic device for closed production of human dendritic cells","authors":"Kevin Loutherback,&nbsp;Peggy Bulur,&nbsp;Allan B. Dietz","doi":"10.1016/j.jcyt.2024.08.009","DOIUrl":"10.1016/j.jcyt.2024.08.009","url":null,"abstract":"<div><div>We have exploited the unique physics available in microfluidic devices to engineer a platform capable of integrating all critical elements of cell therapy into a microfluidic device. The platform can be used to isolate, count, identify and culture cells on a device in a closed Current Good Manufacturing Practice-compatible system. We have used the culture and isolation of human mature dendritic cells (DCs) as our model system, demonstrating each critical element in manufacturing a therapeutic product. We used the system to immunomagnetically isolate CD14+ cells from peripheral blood mononuclear cells, perform on-chip enumeration and surface marker characterization to confirm purity of isolation (mean, 98.6 ± 1.6%) and culture cells in the presence of cytokines to drive differentiation to CD83+ mature DCs. Successful DC maturation was confirmed using on-chip surface marker characterization (positive CD83 expression) with process yields comparable to conventional DC production. The technology presented is the first demonstration of a chip bioreactor capable of recapitulation of all critical elements of cell therapy manufacturing. Its closed nature, scalability and integration of both manufacturing and release testing show the potential for a new approach to industrialization and rapid distribution of cell therapies.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Pages 121-127"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247952","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":"Identification and culture of meniscons, meniscus cells with their pericellular matrix","authors":"Caroline Struijk ,&nbsp;Jasmijn Korpershoek ,&nbsp;Katherine L. Lydon ,&nbsp;Peter Verdonk ,&nbsp;Jozef Michielsen ,&nbsp;Aaron J. Krych ,&nbsp;Lucienne A. Vonk ,&nbsp;Daniel B.F. Saris","doi":"10.1016/j.jcyt.2024.08.006","DOIUrl":"10.1016/j.jcyt.2024.08.006","url":null,"abstract":"<div><h3>Background aims</h3><div>Meniscus injury is highly debilitating and often results in osteoarthritis. Treatment is generally symptomatic; no regenerative treatments are available. “Chondrons,” articular chondrocytes with preserved pericellular matrix, produce more hyaline cartilage extracellular matrix and improve cartilage repair. If meniscons exist in the meniscus and have similar therapeutic potential as chondrons, employing these cells has potential for meniscus cell therapy and tissue engineering. In this study, we isolated and cultured “meniscons,” meniscus cells surrounded by their native pericellular matrix, and investigated cell behavior in culture compared with chondrons.</div></div><div><h3>Methods</h3><div>Human meniscons were enzymatically isolated from osteoarthritic menisci and cultured up to 28 days in fibrin glue. Freshly isolated meniscons and chondrons were analyzed by histology and transmission electron microscopy. We used 5-([4,6-dichlorotriazin-2-yl]amino)fluorescein hydrochloride labeling and type VI collagen immunohistochemistry to image pericellular matrix after 0 and 28 days of culture. Gene expression was quantified using real-time polymerase chain reaction and DNA content and proteoglycan production were analyzed using biochemical assays.</div></div><div><h3>Results</h3><div>Meniscons were successfully isolated from human meniscus tissue. The pericellular matrix of meniscons and chondrons was preserved during 28 days of culture. Meniscons and chondrons had similar cell proliferation and proteoglycan production. Meniscons and chondrons expressed similar levels of collagen type I alpha 1 chain, whereas collagen type II alpha 1 chain and aggrecan expression was lower in the meniscon population.</div></div><div><h3>Conclusions</h3><div>Freshly isolated meniscons and meniscons cultured for 28 days share similarities with chondrons with regard to cell proliferation, morphology and biochemical activity. Rapid isolation of meniscons (45 min) demonstrates potential for one-stage meniscus regeneration and repair, which should be confirmed <em>in vivo</em>.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Pages 98-106"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382214","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":"Enhancing photodynamic and radionuclide therapy by small interfering RNA (siRNA)-RAD51 transfection via self-emulsifying delivery systems (SNEDDS)","authors":"Ulises Paredes-Hernández ,&nbsp;Leslie V. Aguilar-Peña ,&nbsp;Keila Isaac-Olivé ,&nbsp;Blanca Ocampo-García ,&nbsp;Irazú Contreras ,&nbsp;José A. Estrada ,&nbsp;Germán Izquierdo ,&nbsp;Enrique Morales-Avila ,&nbsp;Liliana Aranda-Lara","doi":"10.1016/j.jcyt.2024.08.003","DOIUrl":"10.1016/j.jcyt.2024.08.003","url":null,"abstract":"<div><h3>Background aims</h3><div>Gene-silencing by small interfering RNA (siRNA) is an attractive therapy to regulate cancer death, tumor recurrence or metastasis. Because siRNAs are easily degraded, it is necessary to develop transport and delivery systems to achieve efficient tumor targeting. Self-nanoemulsifying systems (SNEDDS) have been successfully used for pDNA transport and delivery, so they may be useful for siRNA. The aim of this work is to introduce siRNA-RAD51 into a SNEDDS prepared with Phospholipon-90G, Labrafil-M1944-CS and Cremophor-RH40 and evaluate its efficacy in preventing homologous recombination of DNA double-strand breaks caused by photodynamic therapy (PDT) and ionizing radiation (IR).</div></div><div><h3>Methods</h3><div>The siRNA-RAD51 was loaded into SNEDDS using chitosan. Transfection capacity was estimated by comparison with Lipofectamine-2000.</div></div><div><h3>Results</h3><div>SNEDDS(siRNA-RAD51) induced gene silencing effect on the therapies evaluated by cell viability and clonogenic assays using T47D breast cancer cells.</div></div><div><h3>Conclusions</h3><div>SNEDDS(siRNA-RAD51) shown to be an effective siRNA-delivery system to decrease cellular resistance in PDT or IR.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Pages 66-77"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057186","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":"Comprehensive analysis of secretome and transcriptome stability of Wharton jelly mesenchymal stromal cells during good manufacturing practice-compliant production","authors":"Mariana Cañas-Arboleda ,&nbsp;Cristian Camilo Galindo ,&nbsp;Monica Cruz-Barrera ,&nbsp;Katherine Herrera ,&nbsp;Karl Beltrán ,&nbsp;Alejandro Rodríguez ,&nbsp;Björn Rotter ,&nbsp;Bernardo Camacho ,&nbsp;Gustavo Salguero","doi":"10.1016/j.jcyt.2024.08.008","DOIUrl":"10.1016/j.jcyt.2024.08.008","url":null,"abstract":"<div><h3>Background</h3><div>Mesenchymal stromal cells (MSCs) hold promise for cell-based therapies due to their ability to stimulate tissue repair and modulate immune responses. Umbilical cord-derived MSCs from Wharton jelly (WJ) offer advantages such as low immunogenicity and potent immune modulatory effects. However, ensuring consistent quality and safety throughout their manufacturing process remains critical. RNA sequencing (RNA-seq) emerges as a crucial tool for assessing genetic stability and expression dynamics in cell-based therapeutic products.</div></div><div><h3>Methods</h3><div>We examined the secretome and transcriptome of WJ-MSC signatures throughout Good Manufacturing Practice (GMP) production, focusing on the performance of total RNA or Massive Analysis of cDNA Ends (MACE) sequencing.</div></div><div><h3>Results</h3><div>Through extensive transcriptomic analysis, we demonstrated consistent stability of WJ-MSC expression signatures across different manufacturing stages. Notably, MACE-seq showed improved identification of key expression patterns related to senescence and immunomodulation.</div></div><div><h3>Conclusions</h3><div>These findings highlight the potential of MACE-seq as a quality assessment tool for WJ-MSC-based therapies, ensuring their efficacy and safety in clinical applications. Importantly, MACE-seq demonstrated its value in characterizing WJ-MSC-derived products, offering insights that traditional assays cannot provide.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Pages 107-120"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300050","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":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(24)00951-4","DOIUrl":"10.1016/S1465-3249(24)00951-4","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 1","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143147448","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":"A survey of cell processing practices for hematopoietic cell transplantation","authors":"Jesus Fernandez-Sojo ,&nbsp;Joan Cid ,&nbsp;Oscar M. Pello ,&nbsp;María E. Martínez-Muñoz ,&nbsp;Margarita Codinach ,&nbsp;Marta Fonseca-Santos ,&nbsp;Silvia Santos ,&nbsp;Cristina Eguizabal ,&nbsp;Monica Linares ,&nbsp;Nerea Castillo-Flores ,&nbsp;Carmen Azqueta ,&nbsp;Elena Valvidia ,&nbsp;Luis Larrea ,&nbsp;Cell Processing and Advanced Therapies Working Group of the Spanish Society of Blood Transfusion and Cellular Therapy (SETS)","doi":"10.1016/j.jcyt.2024.12.011","DOIUrl":"10.1016/j.jcyt.2024.12.011","url":null,"abstract":"<div><h3>Background</h3><div>There is considerable heterogeneity in cell handling practices for hematopoietic stem cell transplantation in cell processing centers in Spain. The European Directorate for the Quality of Medicines and international standards are not intended to establish best practices or to include all procedures; therefore, each cell processing laboratory must define its own practices and procedures.</div></div><div><h3>Methods</h3><div>A survey was conducted to better understand the differences among cell processing laboratories in Spain in terms of type of facilities and equipment available, service portfolio, staff, informatics systems, product handling, environmental and product quality control tests, batch release criteria, storage and shipping conditions, and criteria for product disposal or recall, to identify areas for harmonization.</div></div><div><h3>Results</h3><div>In this study, 31 authorized centers responded to the survey. Fifteen centers do not usually wash cryopreserved grafts, in contrast to others that perform washing systematically (<em>n</em> = 5) or when the product contains &gt;1 g/kg/dimethyl sulfoxide or recipient body weight is &lt;25 kg (<em>n</em> = 11). We observed high variability in terms of handling of thawed samples, such as in protocols used to enumerate CD34+ cells, compensation solution, temperature and time delay between thawing and CD34+ enumeration. Storage time for cell therapy products varied between 5 and 30 years. Additionally, 12 centers do not reduce plasma before cryopreservation to save space.</div></div><div><h3>Discussion</h3><div>Overall, this survey demonstrates variability in activity, logistics and staff among cell processing laboratories in Spain. Some issues remain ongoing and further efforts should be undertaken to harmonize practices in these facilities, such as indications and procedures for washing cryopreserved stem cells and handling of cryovials to enumerate viable CD34+ cells after thawing. Efforts are needed to regulate product storage to optimize space utilization and reduce associated costs.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 508-515"},"PeriodicalIF":3.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076219","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":"Entering a new era of tumor-infiltrating lymphocyte cell therapy innovation.","authors":"Rodabe N Amaria, Krishna V Komanduri, Adam J Schoenfeld, Giridharan Ramsingh, Rachel A Burga, Madan H Jagasia","doi":"10.1016/j.jcyt.2024.12.010","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.12.010","url":null,"abstract":"<p><p>The therapeutic potential of adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) has been established in advanced melanoma. In February 2024, lifileucel became the first TIL cell therapy to be approved by the FDA and is indicated for adult patients with advanced melanoma. Although the benefit of TIL cell therapy is best characterized in patients with advanced melanoma, several trials are ongoing investigating its safety and efficacy in other solid tumor indications. Nevertheless, wider applicability and adoption of TIL cell therapy will require continued innovation to provide a safer and more efficacious cell therapy product. Several investigational TIL cell therapy products are in preclinical and early clinical development and are applying novel technologies to overcome key challenges. Herein, we summarize the current state of TIL cell therapy and highlight innovations that may reshape its future.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702000","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}