Cytotherapy最新文献

{"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":"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":"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":"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}

{"title":"Considerations for manufacturing of cell and gene medicines for clinical development","authors":"Mark W. Lowdell","doi":"10.1016/j.jcyt.2024.11.015","DOIUrl":"10.1016/j.jcyt.2024.11.015","url":null,"abstract":"<div><div>The global changes from 2001 that elevated substantially modified cell therapies to the definition of “medicinal product” have been the catalyst for the dramatic expansion of the field to its current and future commercial success. Europe was the first to incorporate human somatic cells into drug legislation with the medicines directive of 2001 (2001/83/EC), which led to the development of the term “advanced therapy medicinal products” (ATMPs) to cover all substantially modified products, tissue-engineered products and somatic cells that are not substantially modified but that are used non-homologously. For convenience, I use the term “ATMPs” throughout this review. The transition from “cell therapy” to “cellular medicine” coincided with changes in clinical trial legislation in Europe and, subsequently, across many drug jurisdictions throughout the world. As medicines, there is a clear path through multiple phases of trials and associated requirements for compliance with the good practice standards of drug development, and manufacturability is central to this development.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 874-883"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967399","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":"iPSC-based cell replacement therapy: from basic research to clinical application","authors":"Jun Takahashi","doi":"10.1016/j.jcyt.2025.01.015","DOIUrl":"10.1016/j.jcyt.2025.01.015","url":null,"abstract":"<div><div>The advancement of induced pluripotent stem cell (iPSC) technology has revolutionized regenerative medicine, enabling breakthroughs in disease modeling, drug discovery, and cell replacement therapies. This review examines the progression of iPSC-based regenerative medicine, focusing on cell replacement therapy and mechanisms like the Replacement Effect, which is crucial for long-term tissue regeneration. Using Parkinson's disease as a key example, it discusses the induction of midbrain dopaminergic neurons from iPSCs and the importance of precise signaling for safety and efficacy. By demonstrating the integration and safety of these cells, animal studies have paved the way for clinical trials. This review highlights the need for strategic collaboration among stakeholders—regulatory authorities, research and medical staff, and industry—to ensure successful clinical applications. iPSC technology's ongoing evolution holds significant promise for broader therapeutic applications and improved patient outcomes.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 835-842"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450025","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":"Dark NKnight rising: a current perspective on NK cell and CAR-NK cell therapy","authors":"Joseph R. Caporale ,&nbsp;Meisam Naeimi Kararoudi ,&nbsp;Margaret G. Lamb ,&nbsp;Dean A. Lee","doi":"10.1016/j.jcyt.2025.04.064","DOIUrl":"10.1016/j.jcyt.2025.04.064","url":null,"abstract":"<div><div>Natural killer (NK) cell therapy began decades ago with administration of small doses of minimally-characterized cells known as cytokine-induced or lymphokine-activated killer cells (CIK or LAK, respectively). Methods and conditions that enabled the broad adoption of T cell therapies have often been less effective for NK cells, but in the last 15 years, new NK-specific advances in selection, differentiation, and <em>ex vivo</em> expansion hav e made possible the infusion of large doses of pure and potent NK cell products. Also, NK cells have been more resistant to the genetic modification approaches utilized for engineering T cells, but in the last 5 years several robust approaches for NK cell modification have advanced to the clinic. Thus, a tremendous surge in NK cell clinical trials has been seen recently. Here, we present a focused perspective on the key developments in NK cell therapy that differentiate it from T cell therapies and discuss areas that are key to their clinical and commercial success- both current advancements and hurdles that remain to be addressed.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Pages 812-825"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210115","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(25)00755-8","DOIUrl":"10.1016/S1465-3249(25)00755-8","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 7","pages":"Page A4"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563361","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}