Cytotherapy最新文献

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(25)00770-4","DOIUrl":"10.1016/S1465-3249(25)00770-4","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 8","pages":"Page A5"},"PeriodicalIF":3.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712023","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":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(25)00767-4","DOIUrl":"10.1016/S1465-3249(25)00767-4","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 8","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712020","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":"Improving lung cancer tumor-infiltrating lymphocyte (TIL) manufacturing.","authors":"Pamela K Noldner, Ying Zhou, Liliana Lyniv, Jose R Conejo-Garcia, Scott Antonia, Beth H Shaz","doi":"10.1016/j.jcyt.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.07.001","url":null,"abstract":"<p><strong>Background: </strong>The successful treatment of melanoma using autologous in vitro expanded tumor infiltrating lymphocytes (TILs) has sparked clinical trials for the assessment of TIL efficacy against other cancers, including non-small cell lung cancer (NSCLC). This rise in clinical applications of TILs has increased the need for improved, more streamlined and cost-effective manufacturing protocols. The aim of this study was to simplify and reduce the cost of traditional TIL manufacturing protocols while maintaining GMP manufacturing compliance, yields, and quality of the TIL product.</p><p><strong>Methods: </strong>Resected lung tumors were cultured to expand TILs. In side-by-side experiments, we evaluated media formulations, supplementing reagents, reagent concentrations, TIL activation methods and cryopreservation protocols. The optimizations aim to reduce labor, reagent cost, culture times, and open step manipulations. The resulting TIL products were compared against TILs produced using the Moffitt Cancer Center published protocol. We compared cell yields, viabilities, phenotypes, and TIL cytotoxic activity against matched tumor organoids.</p><p><strong>Results: </strong>TILs were successfully expanded from 35 fragmented tumor samples using T-cell specific media in place of RPMI, human AB serum in place of human platelet lysate and α-CD3/CD28 nanobeads in place of feeder cells for cell activation. Culture duration was reduced from 6 to 7 weeks to 4 weeks and the final product contained an average of 200e9 TILs that were predominantly of the memory phenotype and effectively killed matched tumor cells. While TIL yields and phenotypes were comparable to those produced by the Moffitt Cancer Center protocol, cytotoxicity against matched tumor cells was superior.</p><p><strong>Conclusion: </strong>Traditional TIL manufacturing protocols could be optimized and streamlined into a more cost-effective process for a TIL product that is cytotoxic to tumor cells and yields quantities suitable for clinical studies.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676391","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":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(25)00752-2","DOIUrl":"10.1016/S1465-3249(25)00752-2","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563358","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":"Gene therapy for sickle cell disease: recent advances, clinical trials and future directions","authors":"Josiah Ballantine,&nbsp;John F. Tisdale","doi":"10.1016/j.jcyt.2024.11.006","DOIUrl":"10.1016/j.jcyt.2024.11.006","url":null,"abstract":"<div><div>Sickle cell disease (SCD) is the most common inherited blood disorder worldwide, impacting millions and imposing severe healthcare challenges, particularly in resource-limited regions. Current treatments have variable efficacy and require lifelong adherence. Allogeneic Hematopoietic Stem Cell Transplantation can be curative but comes with significant side effects and limited donor availability limits its widespread applicability. Gene therapy, by addressing the root genetic causes, offers a revolutionary alternative. This article discusses the molecular mechanisms of SCD and β-thalassemia and highlights advancements in gene therapy, such as gene addition via lentiviral vectors and gene editing with CRISPR/Cas9 technology. Clinical trials have brought about significant progress but challenges remain, including leukemogenesis, delivery efficiency and cost. Future efforts must focus on enhancing efficiency, reducing costs, developing nongenotoxic conditioning regimens and methods for <em>in vivo</em> application.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 826-834"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900084","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":"Smart Cell Therapy: an industry perspective on macrophages as living drugs","authors":"David T. Rodgers ,&nbsp;Tatiana Novobrantseva ,&nbsp;Rita N. Barcia","doi":"10.1016/j.jcyt.2024.12.002","DOIUrl":"10.1016/j.jcyt.2024.12.002","url":null,"abstract":"<div><div>Macrophage-based cell therapies represent a cutting-edge frontier in immunotherapy, offering distinct advantages over conventional approaches like CAR-T. This review explores the potential of macrophages to orchestrate both innate and adaptive immune responses, enhancing the body's ability to combat diseases locally and systemically. Dubbed a \"Smart Cell Therapy,\" macrophages can initiate and coordinate complex immunological cascades, leveraging multiple immune system components while also performing effector functions. However, significant challenges persist in developing these therapies, including limited macrophage expansion capacity, inefficient genetic engineering, difficulties with large-scale production, and demonstrating late-stage clinical success. Despite these obstacles, ongoing research and clinical trials indicate that macrophage-based therapies hold immense potential to revolutionize treatment approaches across a spectrum of diseases, from cancer to regenerative medicine. With a focus on industry-led development, this review examines the current landscape of macrophage-based cellular therapies, discussing their promising potential and the substantial hurdles that must be overcome to realize their full therapeutic value.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 849-863"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563224","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 Golden Age of Cell and Gene Therapy","authors":"Edwin M. Horwitz","doi":"10.1016/j.jcyt.2025.04.055","DOIUrl":"10.1016/j.jcyt.2025.04.055","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 791-794"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250663","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 ,&nbsp;Krishna V. Komanduri ,&nbsp;Adam J. Schoenfeld ,&nbsp;Giridharan Ramsingh ,&nbsp;Rachel A. Burga ,&nbsp;Madan H. Jagasia","doi":"10.1016/j.jcyt.2024.12.010","DOIUrl":"10.1016/j.jcyt.2024.12.010","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 864-873"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","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}

{"title":"Overcoming challenges in MSC-sEV therapeutics: insights and advances after a decade of research","authors":"Bernd Giebel ,&nbsp;Sai Kiang Lim","doi":"10.1016/j.jcyt.2025.03.505","DOIUrl":"10.1016/j.jcyt.2025.03.505","url":null,"abstract":"<div><div>Over the past decade, mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) have emerged as promising therapeutics, shifting the focus from MSC engraftment or differentiation to their secretion of sEVs—particularly those under 200 nm—that mediate regenerative and immunomodulatory functions. Transitioning from cell therapies to sEV-based therapies offers clinical advantages, including reduced challenges with cell viability, storage, and administration, and improved pharmacological predictability. However, manufacturing MSC-sEV products faces challenges in defining critical quality attributes (CQAs) for consistent identity and potency. Variability arises from differences in cell sources, culture conditions, enrichment techniques, and the inherent heterogeneity of MSCs. Even the use of immortalized clonal MSC lines may not fully eliminate variability, as factors such as developmental processes, epigenetic modifications, or genetic drift could lead to the re-emergence of heterogeneity. Establishing robust potency CQAs is further complicated by the complex, multimodal modes of action of MSC-sEV products, which involve diverse mechanisms impacting various cell types and processes. Traditional models of EV mediated signalling suggesting direct internalization of sEVs by target cells are increasingly challenged due to inefficient EV-uptake and the high therapeutic efficacy observed. Instead, the Extracellular Modulation of Cells by EVs (EMCEV) model proposes that MSC-sEVs exert their effects by modulating the extracellular environment, enabling a “one EV to many cells” interaction. In conclusion, while MSC-sEV products hold significant therapeutic promise due to their multimodal action and functional redundancy, manufacturing challenges and the complexity of defining potency CQAs remain hurdles to clinical translation. A pragmatic approach focusing on identifying key potency-related CQAs based on specific mechanisms of action—while recognizing that “the process defines the product”—may facilitate the advancement of MSC-sEV therapeutics into clinical applications.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 843-848"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052055","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 next innovations in chimeric antigen receptor T cell immunotherapies for cancer","authors":"Kusala Anupindi ,&nbsp;Julia Malachowski ,&nbsp;Isabella Hodson ,&nbsp;Daniel Zhu ,&nbsp;Carl H. June ,&nbsp;Bruce L. Levine","doi":"10.1016/j.jcyt.2025.05.010","DOIUrl":"10.1016/j.jcyt.2025.05.010","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has transformed cancer treatment and the field of immunotherapy. Although CAR T cell therapy has demonstrated considerable clinical success for the treatment of B cell malignancies, expanding its therapeutic efficacy and accessibility for other hematological malignancies and solid tumors remains a challenge. Key limitations include manufacturing constraints and therapeutic hurdles, such as CAR T cell persistence, proliferation, tumor trafficking and treatment-related toxicities. To overcome the unique challenges associated with CAR T cell therapy, novel technological advancements in CAR design, delivery, and T cell functionality can be leveraged. This review will explore three innovative approaches: gene editing and silencing, armoring strategies and <em>in vivo</em> CAR gene delivery. These approaches are all aimed at enhancing the accessibility and therapeutic efficacy of CAR T cell therapy in hematological malignancies.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 795-811"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340601","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}