Best Practice & Research Clinical Haematology最新文献

{"title":"CAR-NK cells for haematological cancers","authors":"Mohammadamin Noorafrooz ,&nbsp;Robert Peter Gale ,&nbsp;Ramin Noorafrooz ,&nbsp;Sanaz Ghods","doi":"10.1016/j.beha.2025.101631","DOIUrl":"10.1016/j.beha.2025.101631","url":null,"abstract":"<div><div>Chimeric antigen receptor-natural-killer (CAR-NK)-cells are a promising cancer cell therapy. Several features of CAR-NK-cells are suggesting an advantage over CAR-T-cells such as less complex manufacturing, <em>“off-the-shelf</em>” use and lower risks of cytokine release (CRS) and immune effector cell-associated neurotoxicity syndromes (ICANS). CAR-NK-cells derived from several sources are associated with promising pre-clinical and clinical results in haematological cancers. We comprehensively discuss the current landscape of CAR-NK-cell therapy in haematological cancers emphasizing recent progress and future directions. Additionally, we explore the biological mechanisms, engineering and sources of CAR-NK-cells. CAR-NK-cell therapy offers a safe, accessible and efficient option for haematological cancers.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101631"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment in CAR-T cell therapy for lymphoma","authors":"Yuchen Zhu ,&nbsp;Kailin Xu ,&nbsp;Ying Wang","doi":"10.1016/j.beha.2025.101635","DOIUrl":"10.1016/j.beha.2025.101635","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-T cell therapy has proven to be a revolutionizing immunotherapeutic strategy for treating relapsed or refractory lymphoma, achieving remarkable clinical responses. However, there remain some challenges including treatment resistance and early relapse in a minor proportion of patients. The lymphoma tumor microenvironment (TME) is a heterogeneous and dynamic milieu composed of lymphoma cells, immune cells, stromal components, cytokines, and extracellular matrix proteins. CAR-T cell infusion alters the composition of TME and thus impact the endogenous immune response. Additionally, various components of the TME affect the persistence, activity and cytotoxicity of CAR-T cells, which is a key endogenous factor that impeding the efficacy of CAR-T cell therapy in lymphoma. Herein, we review the role of lymphoma TME on CAR-T cells, and discuss strategies targeting TME components to overcome resistance and improve the effectiveness of CAR-T cells.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101635"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cells in hematology: Therapeutic initiatives and future directions","authors":"Portia Smallbone,&nbsp;Partow Kebriaei,&nbsp;Mayela Mendt,&nbsp;Elizabeth J. Shpall,&nbsp;Amanda L. Olson,&nbsp;Warren B. Fingrut","doi":"10.1016/j.beha.2025.101613","DOIUrl":"10.1016/j.beha.2025.101613","url":null,"abstract":"<div><div>In recent years, the landscape of hematology has undergone rapid transformation, driven by innovative therapeutic strategies harnessing the properties of novel cellular therapies. Mesenchymal stem cells (MSCs) represent one of these promising therapies, with potential applications across a range of hematologic conditions. These cells are notable for their immunomodulatory properties, key role in supporting the hematopoietic micro-environment and capacity for multi-directional differentiation. This review will focus on the biologic mechanisms underlying MSC therapeutic use, current avenues of clinical investigation, and potential challenges and future directions for MSC derived therapies.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101613"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-GM-CSF autoantibodies in myeloid leukemias","authors":"Anna Sergeeva,&nbsp;Wingchi K. Leung,&nbsp;Lisa St John,&nbsp;Jeffrey J. Molldrem","doi":"10.1016/j.beha.2025.101611","DOIUrl":"10.1016/j.beha.2025.101611","url":null,"abstract":"<div><div>Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine integral to the differentiation, proliferation, and activation of various immune cells, especially those of myeloid lineage. Recombinant human GM-CSF (rhGM-CSF) plays a critical role after high-dose chemotherapy, hematopoietic cell transplantation, and high-dose irradiation by accelerating myeloid recovery and reducing the risk of severe infections. As an adjuvant in anti-tumor vaccines, rhGM-CSF stimulates the differentiation and activation of dendritic cells and promotes their recruitment to tumor sites.</div><div>Despite the therapeutic benefits, rhGM-CSF can induce the production of anti-GM-CSF-autoantibodies (GM-CSF-Ab) that have been implicated in rare diseases, such as autoimmune pulmonary alveolar proteinosis. These antibodies can neutralize GM-CSF activity, impairing macrophages and neutrophils. Furthermore, anti-GM-CSF-Ab have been linked to myeloid leukemias, where they are associated with active disease. The mechanisms behind anti-GM-CSF-Ab production and their role in disease progression remain poorly understood. This review article provides an overview of GM-CSF and anti-GM-CSF-Ab.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101611"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Creating a GMP cell processing program: A focus on quality and regulation","authors":"Darshan Patel ,&nbsp;Jane Reese Koç ,&nbsp;Folashade Otegbeye","doi":"10.1016/j.beha.2025.101614","DOIUrl":"10.1016/j.beha.2025.101614","url":null,"abstract":"<div><div>Implementing current Good Manufacturing Practice (GMP) regulations and principles even in early phases of cell-based therapy studies is crucial for ensuring safety and reproducible quality of these products. This paper outlines the comprehensive steps necessary to establish a robust GMP-compliant cell processing program in academic programs with emphases on adherence to regulatory and quality standards. While there are different regulatory agencies governing practice across the globe, the prevailing quality principles described here incorporate common requirements and guidelines from agencies such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The goal of this review is to provide guidance for developing a quality management program (QMP) that addresses all critical factors impacting each step in the cell therapy product lifecycle: from procurement and receipt of starter material, through manufacturing, testing, storage, distribution, and administration. The QMP should be designed to assure quality outcomes by maintaining qualified and trained staff at all levels as applicable to their job functions; establishing clear policies and procedures; ensuring the qualification of facilities and equipment; using qualified materials for human use; and providing a framework for detection of trends and implementing process improvement.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101614"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human mesenchymal stem cell therapy: Potential advances for reducing cystic fibrosis infection and organ inflammation","authors":"Tracey L. Bonfield ,&nbsp;Hillard M. Lazarus","doi":"10.1016/j.beha.2025.101602","DOIUrl":"10.1016/j.beha.2025.101602","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Innovation in cystic fibrosis (CF) supportive care, including implementing new antimicrobial agents, improved physiotherapy, and highly effective modulators therapy, has advanced patient survival into the 4th and 5th decades of life. However, even with these remarkable improvements in therapy, CF patients continue to suffer from pulmonary infection and other visceral organ complications associated with long-term deficient cystic fibrosis transmembrane conductance regulator (CFTR) expression. Human mesenchymal stem cells (MSCs) have been utilized in tissue engineering based upon their capacity to provide structural components of mesenchymal tissues. An alternative role of MSCs, however is their versatile utilization as cell-based infusion powerhouses due to the unique capacity to deliver milieu specific soluble biologic factors, promoting immune supportive antimicrobial and anti-inflammatory potency. MSCs derived from umbilical cord blood, bone marrow, adipose and other tissues can be expanded in &lt;em&gt;ex vivo&lt;/em&gt; using good manufacturing procedure facilities for a safe, unique therapeutic to reduce and limit CF infection and facilitate the resolution of multi-organ inflammation. In our efforts, we conducted extensive preclinical development and validation of an allogeneic derived bone marrow derived MSC product in preparation for a clinical trial in CF. In this process, potency models were developed to ensure the functional capacity of the MSC product to provide clinical benefit. &lt;em&gt;In vitro&lt;/em&gt;, murine &lt;em&gt;in vivo&lt;/em&gt; and patient tissue &lt;em&gt;ex vivo&lt;/em&gt; potency models were utilized to follow MSC anti-infective and anti-inflammatory potency associated with the CFTR deficient environment. We showed in our “First in CF” clinical trial that the allogeneic MSCs obtained from healthy volunteer bone marrow samples were safe. The advent of improved CF care measures and exciting new small molecules has changed the survival and morbidity phenotype of patients with CF, however, there are CF patients who cannot tolerate or have genotypes that are non-responsive to modulators. Additionally, even with the small molecule therapy, CF patients are living longer, but without genetic correction, with the CF disease manifestation aggravated by the continuance of pre-existing CFTR-associated clinical issues such as ongoing inflammation. MSCs secrete bio-active factors that enhance and protect tissue function and can promote “self-immune” regulation. These properties can provide therapeutic support for the traditional and changing face of CF disease clinical complications. Further, MSC-derived bio-active factors can directly mitigate colonizing pathogens' survival by producing antimicrobial peptides (AMPs) which change the pathogen surface and increase host recognition, elimination, and sensitivity to antibiotics. Herein, we review the potential of MSC therapeutics for treating many facets of CF, emphasizing the potential for providing great additive ther","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101602"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The history of cytokines and growth factors development","authors":"Smith Kungwankiattichai ,&nbsp;Richard T. Maziarz","doi":"10.1016/j.beha.2025.101612","DOIUrl":"10.1016/j.beha.2025.101612","url":null,"abstract":"<div><div>The discovery and development of cytokines and growth factors represent transformative events in modern medicine, spanning from early observations of immune mediators to current therapeutic applications. This review chronicles the historical progression from the initial identification of permeability factors in 1926 to contemporary engineered cytokine therapeutics. Key milestones include the discovery of interferon (1957), the characterization of colony-stimulating factors, and the development of recombinant proteins in the 1980s. The field has evolved from basic understanding of immune communication to sophisticated therapeutic interventions, including targeted inhibitors and engineered cell therapies. While significant advances have been made in treating various diseases through cytokine modulation, challenges remain in managing pleiotropic effects and optimizing delivery systems. Recent innovations in bioengineering and cell therapy suggest promising directions for future therapeutic applications.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101612"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokines in hematopoietic cell transplantation and related cellular therapies","authors":"Abdul-Hamid Bazarbachi ,&nbsp;Markus Y. Mapara","doi":"10.1016/j.beha.2025.101600","DOIUrl":"10.1016/j.beha.2025.101600","url":null,"abstract":"<div><div>Cytokines are pleiotropic molecules involved in hematopoiesis, immune responses, infections, and inflammation. They play critical roles in hematopoietic cell transplantation (HCT) and immune effector cell (IEC) therapies, mediating both therapeutic and adverse effects. Thus, cytokines contribute to the immunopathology of graft-<em>versus</em>-host disease (GVHD), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). This review examines cytokine functions in these contexts, their influence on engraftment and immune recovery post-transplantation, and their role in mediating toxicities. We focus on current and potential uses of cytokines to enhance engraftment and potentiate IEC therapies, as well as strategies to mitigate cytokine-mediated complications using cytokine blockers (<em>e.g</em>., tocilizumab, anakinra) and JAK inhibitors (<em>e.g</em>., ruxolitinib). We discuss new insights into GVHD physiology that have led to novel treatments, such as CSF1R blockade, which is effective in refractory chronic GVHD.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101600"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR assembly line: Taking CAR T-cell manufacturing to the next level","authors":"Jiasheng Wang ,&nbsp;Paolo F. Caimi","doi":"10.1016/j.beha.2024.101595","DOIUrl":"10.1016/j.beha.2024.101595","url":null,"abstract":"<div><div>The widespread adoption of chimeric antigen receptor (CAR) T-cell therapy has been limited by complex, resource-intensive manufacturing processes. This review discusses the latest innovations aiming to improve and streamline CAR T-cell production across key steps like T-cell activation, genetic modification, expansion, and scaling. Promising techniques highlighted include generating CAR T cells from non-activated lymphocytes to retain a stem-like phenotype and function, non-viral gene transfer leveraging platforms like transposon and CRISPR, all-in-one fully automated bioreactors like the CliniMACS Prodigy and the Lonza Cocoon, rapid CAR T-cell manufacturing via abbreviating or eliminating <em>ex vivo</em> T-cell culture, implementing decentralized point-of-care automated manufacturing platforms, and optimizing centralized bioreactor infrastructure integrating end-to-end automation. Adoption of these emerging technologies can reduce production costs and timelines while enhancing product quality and accessibility. However, significant knowledge gaps persist regarding the feasibility, superiority, and optimal protocols for effectively incorporating many emerging techniques into widespread clinical practice. Further validation through clinical studies is still needed for many of these novel approaches.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101595"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Special issue 37.2 and 37.3 Genetics and Function of HLA and immune-related genes in transplantation and cellular immunotherapy” [Best Pract Res Clin Haematol (2024) 101588]","authors":"Katharina Fleischhauer","doi":"10.1016/j.beha.2024.101594","DOIUrl":"10.1016/j.beha.2024.101594","url":null,"abstract":"","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101594"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}