应用CD19修饰的嵌合抗原受体T细胞治疗淋巴细胞白血病

应用嵌合抗原受体T细胞（chimeric antigen receptor T cell,CAR T）治疗急性和慢性淋巴细胞白血病,在近期已取得了新进展。CAR T细胞是通过将T细胞受体基因和抗CD19抗体基因嵌合,转染至T细胞,在体外扩增以后输注给患者来治疗白血病的新型免疫治疗。经过基因改造后的CAR T细胞的表面具有特异性位点,可以识别淋巴细胞白血病中B细胞表面的CD19抗原。CD19抗原的持续刺激可使CAR T细胞不断增殖与活化,CAR T在患者体内可以增殖1000倍,有效杀伤急性和慢性淋巴细胞白血病细胞。本文就CAR T细胞及其对急性和慢性淋巴细胞白血病的疗效进行综述。     

嵌合抗原受体T细胞治疗恶性血液病的研究进展

嵌合抗原受体(CAR)-T细胞治疗是一种新的免疫疗法.该方法是将识别肿瘤细胞相关抗原的受体与T细胞胞内信号域在体外进行基因重组,再将这些质粒转染至T细胞中,而这类表达CAR的T细胞可特异性识别具有靶抗原的肿瘤细胞并发挥杀伤作用.目前,CAR-T细胞在肿瘤治疗,尤其是在恶性血液病治疗上获得良好疗效,但其疗效、安全性、不良反应、质量控制方面均需进一步验证.笔者拟就CAR-T细胞治疗中的CAR设计、细胞制备、临床试验及不良反应进行综述.     

嵌合抗原受体T细胞治疗T淋巴细胞肿瘤靶点及制备工艺的探索

T淋巴细胞肿瘤是一组高度异质性的血液系统恶性肿瘤,复发和耐药通常是导致治疗失败的主要原因.既往治疗主要采用放化疗,尽管获得较高的治愈率,但仍有相当比例的患者最终治疗失败.随着单克隆抗体、免疫治疗和细胞治疗进入临床实践,恶性血液病的治愈率得到了显著提高.尤其是嵌合抗原受体T细胞(CAR-T)进入临床,其针对B细胞淋巴瘤和...     

嵌合抗原受体T细胞免疫疗法的护理研究进展

嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞免疫疗法是近年来发展非常迅速的一种最先进的细胞免疫治疗技术,在血液系统肿瘤和实体瘤的治疗上取得了显著成效,并展示了良好的应用前景,为肿瘤患者带来了新的希望。由于CAR-T治疗是一项新型的治疗技术,相比以往的细胞免疫治疗风险更高,并发症相对更多,且监测及干预重点均有所不同,对其并发症的早期识别及管理尚处于经验积累阶段。本文就CAR-T细胞免疫疗法的临床应用、常见毒性反应的临床表现及干预策略进行综述,旨在提高临床医护人员对CAR-T细胞免疫疗法相关毒性反应的认知,为有效监测和加强免疫治疗相关毒性反应的管理提供借鉴。     

嵌合抗原受体T细胞治疗的心脏毒性研究进展

嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法是一种新型的免疫疗法,近年来成为肿瘤领域的热点.尤其CD19 CAR-T细胞在难治/复发血液恶性肿瘤治疗中取得显著疗效.然而治疗伴随着明显的毒性,细胞因子释放综合征(CRS)和神经毒性被广泛报道,而心血管毒性定的真实特征及机制仍不清楚....     

嵌合抗原受体T细胞免疫疗法在血液肿瘤治疗中的研究进展

近年来,经过基因工程改造的自体T淋巴细胞疗法在肿瘤治疗的临床试验中取得了令人瞩目的成果,其中嵌合抗原受体T细胞(CAR-T)免疫疗法已经在急性淋巴细胞白血病(ALL)中取得显著的疗效.嵌合抗原受体(CAR)是由抗原结合区与共刺激分子组成的融合分子.而CAR-T具有特异性结合肿瘤细胞的能力.与传统药物不同的是,CAR-T可以凭借免疫记忆效应在体内发挥长期的抗肿瘤作用.因此,CAR-T免疫疗法受到了越来越多的关注,已经成为治疗血液系统肿瘤,尤其是B淋巴细胞恶性肿瘤的极具前景治疗手段.笔者拟就CAR-T免疫疗法在血液系统肿瘤中的研究进展进行综述.     

嵌合抗原受体T细胞治疗恶性淋巴瘤的护理研究进展

从嵌合抗原受体T(CAR-T)细胞的结构及治疗、CAR-T在恶性淋巴瘤中的临床应用、CAR-T细胞输注及不良反应的护理管理等方面进行综述,旨在为护理人员围绕CAR-T治疗制定临床护理方案提供参考。     

嵌合抗原受体T细胞治疗神经系统免疫性疾病临床前景展望

经人工设计的嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)可以特异性清除B细胞,已经较为成熟地应用于治疗B细胞异常增殖的肿瘤性疾病。由于多种自身免疫性疾病与B细胞的异常增殖与活化相关,近年来利用CAR-T治疗自身免疫性疾病受到了广泛关注。本篇综述对CAR-T疗法进行了概述,对其治疗系统性自身免疫疾病的临床经验及机制进行了分析,并总结了CAR-T治疗神经系统免疫性疾病(包括:视神经脊髓炎谱系疾病、多发性硬化、重症肌无力、特发性炎性肌病)的有效性与安全性。分析了CAR-T疗法相较于传统免疫治疗手段的优势与临床应用前景。     

嵌合抗原受体基因修饰T细胞免疫疗法在肺癌治疗中的研究进展

肺癌是全世界所有癌症中发病率和病死率最高的恶性肿瘤之一,目前仍缺乏较好的治疗手段。嵌合抗原受体基因修饰T(CAR-T)细胞免疫疗法作为一种新的治疗方法在血液系统恶性肿瘤中疗效显著,也为肺癌等实体肿瘤的免疫治疗开辟了新途径。然而,由于实体瘤的异质性、肿瘤微环境免疫抑制、肿瘤靶抗原逃逸及脱靶毒性等问题,造成CAR-T细胞免疫疗法在肺癌治疗中的应用存在挑战和障碍。本文总结了CAR-T细胞免疫疗在肺癌治疗中的最新研究进展,包括CAR-T细胞生物学特征、靶点选择、早期临床研究和治疗不良反应,并提出肺癌CAR-T细胞免疫疗法的优化策略,旨在为肺癌的临床免疫治疗提供新思路。     

Belimumab for the management of systemic lupus erythematosus

Introduction: In 2011, Belimumab, a fully humanized monoclonal antibody against B lymphocyte stimulator, became the first biological agent to be licensed by the United States Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) for the use in auto-antibody positive adult Systemic Lupus Erythematosus (SLE).

Areas covered: An overview of the clinical trial data, review of the medical and scientific literature following a MEDLINE search forms the basis of this expert opinion on biological therapy review. The Belimumab International SLE Study Phase III randomized placebo-controlled trials, BLISS-52 and BLISS-76, met the primary endpoint based on the SLE responder index (SRI) at week 52. The trials reported that belimumab 10 mg/kg infusions with standard therapy significantly reduced SLE disease activity compared with placebo with standard therapy.

Expert opinion: The clinical efficacy, safety and tolerability of belimumab indicates a potential role for this drug in achieving disease control, reducing severity of recurrent flares, reducing morbidity and in the long-term achieving a positive long-term impact on quality of life. Belimumab is now being introduced in clinical practice and over the next 5 years data on its use outside the clinical trials will determine its place in SLE management.     

CAR-T细胞构建技术研究进展

嵌合抗原受体T细胞免疫疗法(CAR-T)被认为是最有潜力的癌症治疗方法,并取得了良好的临床疗效.随着CAR-T大规模应用,该技术的局限性也逐渐暴露出来,如治疗效果差 、疾病复发 、不良反应多等.这使得制造结构更优 、安全性更高 、效能更佳的CAR-T细胞成为临床所需.了解CAR-T的制造过程,掌握技术进展,是构建理想的...     

Anti-histones antibodies in systemic lupus erythematosus: prevalence and frequency in neuropsychiatric lupus

To investigate the specificity, sensitivity, and concomitant presence of antibodies against histones (H), histone H1 (H1), and histone H3 (H3) in patients with systemic lupus erythematosus (SLE) and analyze their association with SLE. Serum IgG anti-histones antibodies were detected by enzyme-linked immunosorbent assay in 144 SLE patients consisting of 24 neuropsychiatric lupus (NPSLE), 65 lupus nephritis (LN), and 55 SLE, 100 other rheumatic diseases patients, as well as 40 healthy controls. Clinical and biological parameters of the patients were also evaluated. Anti-H, anti-H1, and anti-H3 antibodies yielded a sensitivity of approximately 33% and a specificity of more than 93% for SLE, which was comparable to that found for anti-double-stranded DNA (anti-dsDNa) antibodies. More significantly, anti-histone antibody is found in approximately 50% of patients with NPSLE compared with LN. Moreover, the titers of anti-histones antibodies of NPSLE patients were significantly higher than that of patients with SLE and LN. The sequential analysis revealed a close correlation of anti-H and anti-H1 antibodies with SLE disease activity. There was an approximate 30% positive rate of anti-histones antibodies in 144 SLE patients lacking anti-nucleosome, anti-mDNA, anti-Sm, and anti-dsDNA antibodies. Antibodies to histones H1 and H3 are markers with high specificity of 93.6-96.4% for SLE. The anti-histone antibody markers are prevalent in approximately 50% of NPSLE. Furthermore, there was a strong correlation with SLE disease activity index and levels of antibodies to histones and H1.     

系统性红斑狼疮患者血清B淋巴细胞刺激因子的水平研究

目的 研究系统性红斑狼疮(SLE)患者血清B淋巴细胞刺激因子(BLyS)蛋白水平,并探讨其与尿蛋白的关系.方法 应用酶联免疫吸附试验(ELISA)法检测尿蛋白阳性组(17例)和尿蛋白阴性SLE患者组(20例)血清Blys水平,以健康志愿者(30例)作为对照.结果 SLE患者血清Blys水平明显高于健康对照组(P＜0.05),但尿蛋白阳性组血清Blys水平与尿蛋白阴性组差异无统计学意义(P＞0.05).结论 SLE患者Blys水平升高,提示BLyS可能与SLE的发病有关.     

嵌合抗原受体T细胞治疗非霍奇金淋巴瘤的最新研究进展

非霍奇金淋巴瘤(NHL)为一组起源于T或B淋巴细胞的恶性肿瘤,约85％均来源于B淋巴细胞.NHL临床与生物学上具有很高的异质性,并且诊断、治疗及预后亦存在很大的差异.随着诊断与治疗水平的提高,大部分NHL患者均可获得长期缓解,但是部分复发/难治性NHL患者的长期生存率仍然不容乐观.近年来,过继细胞免疫治疗(ACT)发展迅猛,尤其是嵌合抗原受体T细胞(CAR-T)在治疗复发/难治性NHL方面进展迅速,其中靶向针对NHL细胞表面的CD19、CD20、CD30等抗原的CAR-T逐步成为治疗NHL的一种全新治疗手段.本文拟从CAR-T的构建、临床治疗NHL的有效性与安全性、性能优化等方面的最新研究进展进行阐述.     

黄芪对红斑狼疮细胞凋亡和T淋巴细胞亚群的影响

目的:研究黄芪对系统性红斑狼疮(SLE)细胞凋亡和T淋巴细胞亚群的影响,探讨其对SLE的治疗作用。方法:将80例初发SLE患者随机分为常规治疗组和黄芪治疗组(常规治疗的基础上加用黄芪注射液)。观察两组患者治疗前后外周血淋巴细胞上Fas、Bcl-2抗原的表达和T淋巴细胞亚群的变化。结果:两组患者治疗后外周血淋巴细胞上Fas抗原的表达下调(P<0.01),Bcl-2抗原的表达以及CD4+亚群、CD4+/CD8+比值上升(P<0.01);其中,治疗后Fas抗原表达的下调、CD4+亚群及CD4+/CD8+比值的上升在黄芪治疗组更显著(P<0.05)。结论:黄芪在一定程度上增加了激素/免疫抑制剂对细胞凋亡的抑制作用,调节T淋巴细胞亚群比例和功能趋于正常,可以作为提高SLE疗效的重要治疗措施。     

系统性红斑狼疮患者多种自身抗体联合检测的临床意义

目的探讨血清抗核抗体(ANA)、抗可溶性抗原(ENA)抗体共16项自身抗体联合检测在系统性红斑狼疮(SLE)诊断中的应用价值。方法收集90例SLE患者、90例风湿性疾病患者和90例健康者血清,采用间接免疫荧光法检测ANA,采用蛋白质免疫印迹法检测其他15项抗体。结果 90例SLE患者ANA、抗核糖体核糖蛋白抗体(抗nRNP)、抗Smith抗体(抗Sm)、抗干燥综合征A抗体(抗SSA)、抗Ro-52抗体、抗双链DNA抗体(抗ds-DNA)、抗核小体抗体(AnuA)、组蛋白(AHA)和抗核糖体P蛋白抗体(ARPA)检测阳性率分别为97.8%、56.7%、33.3%、77.8%、70.0%、35.6%、38.9%、33.3%和43.3%,均高于风湿性疾病患者组和健康对照组,差异有统计学意义(P<0.05)。ANA灵敏度、阴性预测值最高,特异性最低。除ANA以外,抗nRNP/Sm、ARPA、AnuA、抗SSA、抗ds-DNA、抗Sm的正确指数均较高。抗Sm、抗ds-DNA、AnuA、ARPA、抗nRNP/Sm特异性及阳性预测值较高,此5种自身抗体具有互补关系。结论 ANA因灵敏度高,特异性低,只适宜作为SLE的筛选指标。抗Sm、抗ds-DNA、AnuA、ARPA、抗nRNP/Sm对SLE具有较高的特异性,与ANA联合检测可互相弥补其缺陷,有利于SLE的诊断和治疗。     

Targeting B cells with biologics in systemic lupus erythematosus

Importance of the field: The use of biologics as immune modulators in several autoimmune diseases has provided new tools to the physician's therapeutic armamentiarium and has led to improved patients' outcomes and quality of life. By producing autoantibodies, B cells in systemic lupus erythematosus (SLE) are key players in the pathogenesis of the disease and in its clinical manifestations. Therefore, biologics that target B cells in SLE aim at reducing the activity of these cells for the induction of remissions and/or amelioration of disease activity, reduction of organ involvement, and limitation of the complications and side effects caused by immunosuppressive therapies.

Areas covered in this review: This review describes the past and current clinical trials with B-cell-targeted biologics in SLE, to provide a historical perspective and the state-of-the-art on the topic.

What the reader will gain: We review how the disappointment in the field from promising agents has been instrumental in providing valuable lessons leading to an improved design of new trials that are now giving encouraging results.

Take home message: In systemic lupus erythematosus (SLE), the use of B-cell-based biologics in clinical trials has shown both disappointment and promise.     

狼疮带试验对诊断系统性红斑狼疮的意义

目的　探讨狼疮带试验 (LBT)在系统性红斑狼疮 (SLE)诊断中的意义。方法 :对 15 0例SLE患者和 5 0例非SLE患者分别检测血清ANA、ds-DNA、补体、免疫球蛋白、尿素氮、肌酐、尿蛋白定性及定量、肾脏组织病理、LBT免疫成分。结果　LBT在SLE诊断中的敏感性为 71%、特异性为 84 %、阳性预测值为 93%、阴性预测值为 4 8% ,LBT阳性与肾损害及狼疮活动关系密切。结论　LBT是SLE的诊断的一项重要辅助指标