Best Practice & Research Clinical Haematology最新文献

英文中文

Therapeutic initiatives using mesenchymal stem cells and other novel cells in hematology 利用间充质干细胞和其他血液新细胞的治疗方案

IF 2.2 4区医学 Q3 HEMATOLOGY

Best Practice & Research Clinical Haematology

Pub Date : 2025-05-21 DOI: 10.1016/j.beha.2025.101636

Leland Metheny MD (Associate Professor)

引用次数: 0

Immune reconstitution following allogeneic hematopoietic cell transplantation and CAR-T therapy: dynamics, determinants, and directions 同种异体造血细胞移植和CAR-T治疗后的免疫重建：动力学、决定因素和方向

IF 2.2 4区医学 Q3 HEMATOLOGY

Best Practice & Research Clinical Haematology

Pub Date : 2025-05-16 DOI: 10.1016/j.beha.2025.101634

Weijia Fu , Jiahao Chen , Xiaoxia Hu

Immune reconstitution (IR) is a dynamic and sequential process that occurs after allogeneic hematopoietic cell transplantation (allo-HCT) and cellular therapies, involving the gradual recovery of both innate and adaptive immune compartments. The success of IR is a critical determinant of clinical outcomes, including the risk of graft-versus-host disease and graft-versus-leukemia effects. In the context of allo-HCT, IR shaped by various factors, including transplantation modalities, conditioning regimens, therapeutic interventions, and post-transplant strategies. The kinetics and quality of IR following chimeric antigen receptor T-cell (CAR-T) therapy are also shaped by several factors, such as lymphodepleting chemotherapy, CAR construct design, and the patient's baseline immune status. In particular, B-cell–targeted CAR-T therapy frequently results in B-cell aplasia, hypogammaglobulinemia, and immune exhaustion, necessitating improved monitoring and post-treatment interventions. These immunologic effects highlight the need for improved post-treatment monitoring and supportive interventions to reduce infection risk and ensure sustained immune recovery. To better characterize IR across both allo-HCT and CAR-T settings, advanced immune profiling technologies, such as flow cytometry and single-cell RNA sequencing, are providing new insights into the dynamics of immune recovery. Here, we summarize current knowledge on IR kinetics and evaluate the impact of different transplant and CAR-T settings. We then discuss personalized strategies to optimize immune monitoring and therapeutic approaches for recipients of allo-HCT and CAR-T therapies.

免疫重建（IR）是异基因造血细胞移植和细胞治疗后发生的一个动态和连续的过程，涉及先天和适应性免疫室的逐渐恢复。IR的成功是临床结果的关键决定因素，包括移植物抗宿主病和移植物抗白血病效应的风险。在同种异体hct的背景下，IR受多种因素影响，包括移植方式、调理方案、治疗干预和移植后策略。嵌合抗原受体t细胞（CAR- t）治疗后IR的动力学和质量也受到几个因素的影响，如淋巴细胞消耗化疗、CAR结构设计和患者的基线免疫状态。特别是，b细胞靶向CAR-T治疗经常导致b细胞发育不全、低γ -球蛋白血症和免疫衰竭，需要改进监测和治疗后干预。这些免疫效应强调需要改进治疗后监测和支持性干预措施，以降低感染风险并确保持续的免疫恢复。为了更好地表征同种异体hct和CAR-T环境下的IR，先进的免疫分析技术，如流式细胞术和单细胞RNA测序，正在为免疫恢复的动态提供新的见解。在这里，我们总结了目前关于IR动力学的知识，并评估了不同移植和CAR-T设置的影响。然后，我们讨论个性化的策略，以优化免疫监测和治疗方法，为接受同种异体hct和CAR-T治疗。

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引用次数: 0

Research progress of targeted BCMA CAR-T therapy for relapsed/refractory multiple myeloma antigen-negative relapse 靶向BCMA CAR-T治疗复发/难治性多发性骨髓瘤抗原阴性复发的研究进展

IF 2.2 4区医学 Q3 HEMATOLOGY

Best Practice & Research Clinical Haematology

Pub Date : 2025-05-15 DOI: 10.1016/j.beha.2025.101632

Lulu Kong , Kailin Xu , Wei Chen

Chimeric antigen receptor T cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has emerged as a novel and effective modality for the treatment of relapsed or refractory multiple myeloma (RRMM), achieving remarkable therapeutic outcomes. However, relapse remains a major problem impeding the long-term efficacy of this therapy, with antigen-negative relapse being a particularly challenging issue. The mechanisms underlying BCMA antigen-negative relapse encompass a spectrum of phenomena, including diminished or lost tumor antigen expression, BCMA shedding, impaired antigen presentation, trogocytosis, antigen mutations, and alternative splicing. To overcome the problem of antigen-negative relapse in BCMA CAR-T therapy, a variety of strategies are being explored. These include dual/multi-specific CAR-T cell therapy, combination therapies with antibody-drug conjugates (ADCs) or bispecific T-cell engagers (BiTEs), integration with hematopoietic stem cell transplantation (HSCT), identification of novel targets, and the development of innovative cell therapies such as CAR-NK and CAR-M (CAR-Macrophage). Additionally, the optimization of CAR-T cells through gene editing technologies to enhance their durability and anti-tumor activity is a burgeoning area of research. In future, targeted BCMA CAR-T therapy is poised to place greater emphasis on individualization and precision medicine, combining multiple therapeutic approaches to reduce the incidence of relapse, thereby improving treatment efficacy and longevity.

靶向b细胞成熟抗原（BCMA）的嵌合抗原受体T细胞（CAR-T）治疗已成为治疗复发或难治性多发性骨髓瘤（RRMM）的一种新颖有效的治疗方式，取得了显著的治疗效果。然而，复发仍然是阻碍这种治疗长期疗效的主要问题，抗原阴性复发是一个特别具有挑战性的问题。BCMA抗原阴性复发的机制包括一系列现象，包括肿瘤抗原表达减少或丢失、BCMA脱落、抗原呈递受损、巨噬细胞增多、抗原突变和选择性剪接。为了克服BCMA CAR-T治疗中抗原阴性复发的问题，人们正在探索各种策略。这些包括双/多特异性CAR-T细胞治疗，与抗体-药物偶联物（adc）或双特异性t细胞接合物（BiTEs）的联合治疗，与造血干细胞移植（HSCT）的整合，新靶点的鉴定，以及创新细胞疗法如CAR-NK和CAR-M （car -巨噬细胞）的开发。此外，通过基因编辑技术优化CAR-T细胞以增强其耐久性和抗肿瘤活性是一个新兴的研究领域。未来，靶向BCMA CAR-T治疗将更加注重个体化和精准医疗，结合多种治疗方法降低复发率，从而提高治疗效果和延长治疗寿命。

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引用次数: 0

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 Q3 HEMATOLOGY

Best Practice & Research Clinical Haematology

Pub Date : 2025-05-15 DOI: 10.1016/j.beha.2025.101633

Yan Xu, Jianping Mao

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.

嵌合抗原受体T （CAR-T）细胞疗法是一种精确的免疫疗法，虽然受到抗原逃逸、肿瘤微环境（TME）抑制和CAR-T细胞耗竭的限制，但在治疗某些类型的癌症方面显示出良好的效果。分子靶向药物可以通过靶向肿瘤的关键信号转导来增强抗癌效果，为优化CAR-T细胞治疗提供了线索。此外，分子靶向药物协同协助CAR-T细胞转化TME，增强抗癌活性，抑制免疫逃逸。它们的结合迅速成为多发性骨髓瘤（MM）个体化治疗研究的焦点。在本综述中，我们描述了在CAR-T细胞联合治疗MM中常用的分子靶向药物。

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 Q3 HEMATOLOGY

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

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, “off-the-shelf” 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.

嵌合抗原受体-自然杀伤细胞（CAR-NK）是一种很有前途的肿瘤细胞治疗方法。car - nk细胞的几个特征表明它比car -t细胞有优势，如制造过程更简单、“现成”使用、细胞因子释放（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）的风险更低。来自多种来源的car - nk细胞与血液学癌症的临床前和临床结果有关。我们全面讨论了car - nk细胞治疗血液病癌症的现状，强调了最近的进展和未来的方向。此外，我们还探讨了car - nk细胞的生物学机制、工程和来源。car - nk细胞疗法为血液学癌症提供了一种安全、可及和有效的治疗选择。

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 Q3 HEMATOLOGY

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

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.

过继细胞疗法，或收集和转移免疫细胞给患者，正在成为许多恶性肿瘤的治疗选择，特别是血液恶性肿瘤，在实体瘤和非恶性疾病（如自身免疫性疾病）中发挥越来越大的作用。先天免疫细胞自然杀伤（NK）细胞的过继性转移是一种独特的潜在治疗方法，可以单独治疗癌症患者，也可以作为其他免疫靶向治疗的辅助治疗方法，与其他细胞治疗方法（如T细胞）相比具有一些优势。我们回顾了NK细胞作为人类疾病治疗的关键概念，并讨论了使用NK细胞治疗恶性肿瘤的关键试验。

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 Q3 HEMATOLOGY

Best Practice & Research Clinical Haematology

Pub Date : 2025-05-15 DOI: 10.1016/j.beha.2025.101635

Yuchen Zhu , Kailin Xu , Ying Wang

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.

嵌合抗原受体(CAR)-T细胞疗法已被证明是一种革命性的治疗复发或难治性淋巴瘤的免疫治疗策略，取得了显著的临床疗效。然而，仍存在一些挑战，包括少数患者的治疗耐药性和早期复发。淋巴瘤肿瘤微环境（TME）是由淋巴瘤细胞、免疫细胞、基质成分、细胞因子和细胞外基质蛋白组成的异质性动态环境。CAR-T细胞输注改变TME的组成，从而影响内源性免疫反应。此外，TME的各种成分影响CAR-T细胞的持久性、活性和细胞毒性，这是阻碍CAR-T细胞治疗淋巴瘤疗效的关键内源性因素。本文综述了淋巴瘤TME对CAR-T细胞的作用，并讨论了针对TME成分克服耐药性和提高CAR-T细胞有效性的策略。

引用次数: 0

Cytokines in hematology, hematopoietic cell transplantation and immune effector cell therapy: Preface 细胞因子在血液学、造血细胞移植和免疫效应细胞治疗中的应用：前言

IF 2.2 4区医学 Q3 HEMATOLOGY

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

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 Q3 HEMATOLOGY

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

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.

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.

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.

移植耐受是一种免疫状态，在这种状态下，移植受体的免疫系统不会对同种异体移植物产生破坏性的免疫反应。耐受性提供了终身免疫抑制的另一种选择，通过减少移植相关的发病率，可能延长同种异体移植和患者的生存时间。目前，实现同种异体移植物耐受的唯一临床相关方法依赖于通过骨髓或造血细胞移植诱导供体造血嵌合。有两种已知的T细胞对异体抗原的耐受性-中央和外周。在中枢耐受中，同种异体抗原呈递胸腺髓质导致同种异体反应性未成熟淋巴细胞的克隆性缺失。外周耐受是由外周耐受细胞群的发育介导的，如未成熟的树突状细胞和调节性T细胞，它们抑制或删除外周的同种异体反应性免疫细胞。细胞因子作为免疫细胞分泌的调节免疫反应的信号分子，在中枢和外周耐受的发展中都起着重要作用，在介导同种异体移植排斥和耐受中都起着关键作用。了解细胞因子对免疫系统影响的免疫学基础可以帮助我们更好地理解它们在耐受中的作用，并利用这种理解更可靠、更安全地诱导移植耐受。

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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 Q3 HEMATOLOGY

Best Practice & Research Clinical Haematology

Pub Date : 2025-05-08 DOI: 10.1016/j.beha.2025.101628

Alexandra Haugh, Matthew J. Frigault

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.

细胞因子在促进免疫效应细胞（IEC）治疗的疗效和形成独特的相关毒性谱（包括CRS、ICANS和IEC- hs）方面发挥着不可或缺的作用。我们回顾了在IEC制造过程中使用的各种细胞因子，以及内源性细胞因子在细胞输注后促进成功扩增和活性的作用。我们讨论了重组外源性细胞因子在进一步促进T细胞活性中的作用，以及下一代IEC产品，这些产品旨在表达以自主方式发出信号的细胞因子。最后，我们讨论了几种iec相关毒性的工作模型，强调了细胞因子在驱动这些毒性中的关键作用，以及抗细胞因子治疗的干预措施来克服它们。

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全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

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