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Applications and prospects of molecularly targeted drugs combined with CAR-T cell therapy to treat multiple myeloma 分子靶向药物联合CAR-T细胞治疗多发性骨髓瘤的应用与展望
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-15 DOI: 10.1016/j.beha.2025.101633
Yan Xu, Jianping Mao
{"title":"Applications and prospects of molecularly targeted drugs combined with CAR-T cell therapy to treat multiple myeloma","authors":"Yan Xu,&nbsp;Jianping Mao","doi":"10.1016/j.beha.2025.101633","DOIUrl":"10.1016/j.beha.2025.101633","url":null,"abstract":"<div><div>Chimeric antigen receptor T (CAR-T) cell therapy, a type of precision immunotherapy, has shown promising outcomes in treating certain types of cancers, although limited by the antigen escape, suppression on the tumor microenvironment (TME), and CAR-T cell depletion. Molecularly targeted drugs can enhance the anti-cancer efficacy by targeting key signal transductions against cancers, providing a clue for optimizing the CAR-T cell therapy. Moreover, molecularly targeted drugs synergistically assist CAR-T cells to transform the TME, boost anti-cancer activities and inhibit immune escape. Their combination has rushed into the spotlight of research on individualized treatments for multiple myeloma (MM). In the present review, we described frequently used molecularly targeted drugs in the combination of CAR-T cell therapy against MM.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101633"},"PeriodicalIF":2.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106977","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}
引用次数: 0
CAR-NK cells for haematological cancers CAR-NK细胞用于血液学癌症
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-15 DOI: 10.1016/j.beha.2025.101631
Mohammadamin Noorafrooz , Robert Peter Gale , Ramin Noorafrooz , Sanaz Ghods
{"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":"2025-05-15","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}
引用次数: 0
Natural born Killers: Harnessing NK cells to treat cancer 天生杀手：利用NK细胞治疗癌症
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-15 DOI: 10.1016/j.beha.2025.101630
Kanchi Patell , Katherine Myers , Amr Mohamed , David Wald , J. Eva Selfridge
{"title":"Natural born Killers: Harnessing NK cells to treat cancer","authors":"Kanchi Patell ,&nbsp;Katherine Myers ,&nbsp;Amr Mohamed ,&nbsp;David Wald ,&nbsp;J. Eva Selfridge","doi":"10.1016/j.beha.2025.101630","DOIUrl":"10.1016/j.beha.2025.101630","url":null,"abstract":"<div><div>Adoptive cellular therapy, or the collection and transfer of immune cells to patients, is emerging as a treatment option for many malignancies, especially hematologic malignancies, with a growing role in solid tumors and non-malignant conditions such as autoimmune diseases. The adoptive transfer of the innate immune cell natural killer (NK) cells is uniquely poised as a potential therapy alone or as an adjunct to other immune-targeted therapies for patients with cancer, with several advantages over other cell therapies such as T cells. We review key concepts in NK cells as a therapy for human disease and discuss key trials using NK cells in malignancy.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 3","pages":"Article 101630"},"PeriodicalIF":2.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169070","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}
引用次数: 0
Tumor microenvironment in CAR-T cell therapy for lymphoma CAR-T细胞治疗淋巴瘤的肿瘤微环境
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-15 DOI: 10.1016/j.beha.2025.101635
Yuchen Zhu , Kailin Xu , Ying Wang
{"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":"2025-05-15","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}
引用次数: 0
Cytokines in hematology, hematopoietic cell transplantation and immune effector cell therapy: Preface
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-10 DOI: 10.1016/j.beha.2025.101629
Thomas R. Spitzer MD, Hillard M. Lazarus MD, FACP, Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, FRCPI(hc), FRSM
{"title":"Cytokines in hematology, hematopoietic cell transplantation and immune effector cell therapy: Preface","authors":"Thomas R. Spitzer MD,&nbsp;Hillard M. Lazarus MD, FACP,&nbsp;Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, FRCPI(hc), FRSM","doi":"10.1016/j.beha.2025.101629","DOIUrl":"10.1016/j.beha.2025.101629","url":null,"abstract":"","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101629"},"PeriodicalIF":2.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942283","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}
引用次数: 0
Cytokines in transplantation tolerance 细胞因子在移植耐受中的作用
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-08 DOI: 10.1016/j.beha.2025.101627
Andre Souffrant , Avery Wilson , Bryar Hansen , Katsuhiro Tomofuji , Ryo Otsuka , Gilles Benichou , Thomas Spitzer , Tatsuo Kawai
{"title":"Cytokines in transplantation tolerance","authors":"Andre Souffrant ,&nbsp;Avery Wilson ,&nbsp;Bryar Hansen ,&nbsp;Katsuhiro Tomofuji ,&nbsp;Ryo Otsuka ,&nbsp;Gilles Benichou ,&nbsp;Thomas Spitzer ,&nbsp;Tatsuo Kawai","doi":"10.1016/j.beha.2025.101627","DOIUrl":"10.1016/j.beha.2025.101627","url":null,"abstract":"<div><div>Transplantation tolerance is an immunologic state in which a transplant recipient's immune system does not mount a destructive immune response to an allograft. Tolerance offers an alternative to lifelong immunosuppression, potentially extending both allograft and patient survival by reducing transplant-related morbidity. Currently, the only clinically relevant approaches to achieve allograft tolerance rely on induction of donor hematopoietic chimerism through bone marrow or hematopoietic cell transplantation.</div><div>There are two known types of T cell tolerance to alloantigens – central and peripheral. In central tolerance, alloantigen presentation in the thymic medulla results in clonal deletion of alloreactive immature lymphocytes. Peripheral tolerance is mediated by development of tolerogenic cell populations such as immature dendritic cells and regulatory T cells which suppress or delete alloreactive immune cells in the periphery.</div><div>As the signaling molecules secreted by immune cells to orchestrate immune responses, cytokines are important in development of both central and peripheral tolerance and are critical in mediating both allograft rejection and tolerance. Understanding the immunology underlying the effects of cytokines on the immune system can help us to better understand their role in tolerance and to leverage that understanding to more reliably and safely induce transplantation tolerance.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101627"},"PeriodicalIF":2.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130798","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}
引用次数: 0
Cytokines and immune effector cell therapy 细胞因子和免疫效应细胞疗法
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-08 DOI: 10.1016/j.beha.2025.101628
Alexandra Haugh, Matthew J. Frigault
{"title":"Cytokines and immune effector cell therapy","authors":"Alexandra Haugh,&nbsp;Matthew J. Frigault","doi":"10.1016/j.beha.2025.101628","DOIUrl":"10.1016/j.beha.2025.101628","url":null,"abstract":"<div><div>Cytokines play an integral role in both promoting the efficacy of immune effector cell (IEC) therapies and in the development of the unique spectrum of associated toxicities, including CRS, ICANS, and IEC-HS. We review the various cytokines that have been employed in the IEC manufacturing process as well as the role of endogenous cytokines in promoting successful expansion and activity following cell infusion. We discuss the role of recombinant exogenous cytokines in further promoting T cell activity, as well as next-generation IEC products engineered to express cytokines that signal in an autonomous fashion. Finally, we discuss working models of several IEC-associated toxicities, highlighting the crucial role of cytokines in driving these toxicities, as well as interventions with anti-cytokine therapies to overcome them.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101628"},"PeriodicalIF":2.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068242","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}
引用次数: 0
Advancing MSC therapy: The next generation of potent mesenchymal stromal cells for systemic autoimmune rheumatic diseases 推进MSC治疗：下一代强效间充质间质细胞治疗系统性自身免疫性风湿病
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-05-02 DOI: 10.1016/j.beha.2025.101626
Hulya Bukulmez , Kristin B. Highland , Rujman Khan , Gary S. Gilkeson , Steven N. Emancipator
{"title":"Advancing MSC therapy: The next generation of potent mesenchymal stromal cells for systemic autoimmune rheumatic diseases","authors":"Hulya Bukulmez ,&nbsp;Kristin B. Highland ,&nbsp;Rujman Khan ,&nbsp;Gary S. Gilkeson ,&nbsp;Steven N. Emancipator","doi":"10.1016/j.beha.2025.101626","DOIUrl":"10.1016/j.beha.2025.101626","url":null,"abstract":"<div><div>Fields that deal with systemic autoimmune diseases such as rheumatology, gastroenterology, and endocrinology have adopted the principles of immune modulation, including shifting immune activation sates, from advances originally developed in oncology. Most clinical trials to date have demonstrated efficacy of cell therapies primarily in in hematologic and solid tumors, largely driven by chimeric antigen receptor T (CAR-T) cells. In contrast, mesenchymal stromal cells (MSCs) have shown limited success in oncology applications.</div><div>In this article we review the most recent clinical trials involving MSCs and their promising results for patients with systemic autoimmune rheumatic diseases that have failed to respond to standard of care (SOC) therapies.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101626"},"PeriodicalIF":2.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922304","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}
引用次数: 0
Endogenous and exogenous cytokines: An overview and introduction 内源性和外源性细胞因子：概述和介绍
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-04-13 DOI: 10.1016/j.beha.2025.101615
Thomas R. Spitzer , Hillard M. Lazarus
{"title":"Endogenous and exogenous cytokines: An overview and introduction","authors":"Thomas R. Spitzer ,&nbsp;Hillard M. Lazarus","doi":"10.1016/j.beha.2025.101615","DOIUrl":"10.1016/j.beha.2025.101615","url":null,"abstract":"<div><div>Cytokines are ubiquitous small proteins, secreted by virtually all leukocytes and other immune effector cells, that interact with other cytokines and effector and regulatory cells to direct innate and adaptive immunity. Six broad categories of cytokines have been described, with functions ranging from stimulation of immunity and inflammation by cytokines produced by white blood cells (interleukins) to impacting the migration of immune effector cells to sites of inflammation and tissue injury (chemokines). When secreted in excess, or when there exists an imbalance between proinflammatory and anti-inflammatory cytokines, diseases ranging from sepsis to organ transplant rejection to autoimmune disorders occur. The development of exogenous cytokines for therapeutic use, similar or identical to naturally occurring cytokines, has resulted in advances in the management of cancer and autoimmune diseases. On the other hand, the development of inhibitors of cytokines has resulted in the ability to control of a growing list of inflammatory, neoplastic, autoimmune, and allergic conditions. Future investigations should continue to explore the manner cytokines are exploited for therapeutic purpose or are used as inhibitors to interrupt the pathobiological mechanisms of disease.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101615"},"PeriodicalIF":2.2,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844629","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}
引用次数: 0
Mesenchymal stem cells in hematology: Therapeutic initiatives and future directions 间充质干细胞在血液学中的应用：治疗举措和未来方向
IF 2.2 4区 医学
Best Practice & Research Clinical Haematology Pub Date : 2025-03-01 DOI: 10.1016/j.beha.2025.101613
Portia Smallbone, Partow Kebriaei, Mayela Mendt, Elizabeth J. Shpall, Amanda L. Olson, Warren B. Fingrut
{"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}
引用次数: 0
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