单克隆抗体在恶性血液病治疗中的应用

近年来，应用单克隆抗体(单抗)治疗恶性血液病发展迅猛，目前已有5种单抗获美国FDA批准用于临床，另外尚有许多单抗正在进行各期临床试验：根据单抗是否连接其他物质分为未结合型、抗癌药物结合型及放射性核素结合型三大类，现分述如下。     

恶性血液病相关性肌少症研究进展

对恶性血液病相关性肌少症的患病率、危险因素、不良影响、评估工具及治疗进行综述,以期为临床医护人员选择合适的评估工具、采取有效措施提供依据。     

丙戊酸治疗恶性血液病的研究进展

丙戊酸通过抑制组蛋白去乙酰化酶(HDAC)的活性,特异性降解HDAC2,以及caspase依赖及非依赖途径诱导凋亡,在恶性血液病中的治疗作用越来越受到重视。本文就丙戊酸治疗恶性血液病的机制及目前进行的临床研究作一综述。     

抗CD45单克隆抗体在恶性血液病治疗中的研究进展

CD45分子广泛表达于各种造血细胞表面,在淋巴细胞发育、T细胞活化和细胞信号转导等多个方面发挥着重要作用.目前其单克隆抗体主要应用于血液系统疾病的免疫分型检测;在恶性血液病治疗方面,已有文献报道抗CD45单抗可有效清除淋巴细胞、抑制排斥反应和诱导免疫耐受,同时作为载体与各种偶联物联合发挥靶向抗肿瘤作用.     

免疫毒素治疗恶性血液病

免疫毒素导向治疗恶性血液病、尤其是白血病和淋巴瘤是一种非常具有吸引力的尝试性研究。动物实验研究结果表明，免疫毒素导向治疗恶性血液病取得了较为理想的疗效。     

恶性血液病患者社会支持研究进展

恶性血液病是一组恶性程度高、治疗过程复杂、预后较差的恶性肿瘤,对生命和健康的危害很大,对其社会活动以及家庭生活、经济诸多方面均带来损害。本文通过回顾恶性血液病患者社会支持研究现状,旨在协助患者优化其社会支持网络,为其提供良好的社会支持,以减轻患者的生理痛苦和精神压力,避免不良情绪和事件发生,使其处于治疗护理最佳身心状态,按时、愉快地接受治疗,从而提高生活质量,延长生存期。     

恶性血液病去甲基化治疗的研究进展

DNA甲基化是一种在DNA序列不变情况下的DNA生物修饰方式。一般来说,基因表达水平与DNA甲基化呈负相关,异常CpG岛的甲基化可诱导基因沉默。去甲基化治疗就是用药物清除启动区的甲基,使因高甲基化而关闭的抑癌基因重新表达,达到治疗肿瘤的目的。去甲基化治疗作为一种新的治疗途径可能对防止恶性血液病化疗耐药及复发有一定作用。本文对DNA甲基化的机制、DNA甲基化异常与恶性血液病的关系、DNA去甲基化治疗的机理以及恶性血液病（急性、慢性白血病、淋巴瘤以及骨髓增生异常综合征）去甲基化治疗的研究进展进行了综述。     

重视部分恶性血液病血型血清学检查异常特征

由于血液不是1个定形的器官,而是以液体形式不停地在人体体内循环,灌注着机体每个器官与组织的微循环,也就决定了血液或造血器官发生病理变化时,可能会引起机体血型血清学发生变化,特别是部分恶性血液病引起的血型血清学检查异常特征尤为多见,应予以高度的重视.     

免疫毒素治疗恶性血液病

免疫毒素导向治疗恶性血液病、尤其是白血病和淋巴瘤是一种非常具有吸引力的尝试性研究。动物实验研究结果表明,免疫毒素导向治疗恶性血液病取得了较为理想的疗效。     

美罗华治疗原发性巨球蛋白血症不良反应

1 病历摘要 女,60岁.头晕、乏力、排酱油色尿3个月余,恶心呕吐半个月于2010-06-22人我院.该患于2010-03感冒后出现头晕、乏力伴心悸、胸闷.排酱油色尿,自述受凉后面部出现水泡,皮肤较前易冻伤,温度升高后可缓解.病程中不伴骨关节痛、皮肤黏膜出血,不伴视物模糊、体重下降.2010-04就诊于中医药大学,经相关检查诊断为溶血性贫血,给予中药治疗(具体经过不详)2个月余,病情稍缓解,尿色变浅后出院.     

抗人CD20单克隆抗体治疗B细胞淋巴瘤研究进展

近年来,对B细胞淋巴瘤的抗原靶向性治疗已取得了巨大进展。出现了一种新的非常有发展前景的治疗方法。即以B细胞分化抗原CD20为靶抗原的单克隆抗体（McAb)疗法。CD20是非糖基化的跨膜磷酸蛋白,分子质量为35kD。表达在大多数成熟B细胞表达,分化为浆细胞后,CD20表达消失。CD20可能参与B细胞成熟与分化的调节,作为钙离子通道发挥某些生物学作用。更为重要的是,95%以上的B细胞淋巴瘤表达CD20,且无显内化及脱落,这些特点使其成为单克隆抗体疗法的理想靶抗原,临床试验结果表明,抗CD20单克隆抗体既可单独应用,亦可作为放射性同位素或细胞毒制剂的载体,其疗效显,且使用安全,副反应小,许多研究报道已阐明了抗CD20单克隆抗体治疗B细胞淋巴瘤的几种可能的效应机制。目前,人们正致力于探索一些新的治疗策略以期提高这种疗法的特异性,减少其非特异性的毒副作用。     

Ultrasound-Enhanced Monoclonal Antibody Production

With the rapidly growing demand for monoclonal antibody (mAb)–based products, new technologies are urgently needed to increase mAb production while reducing manufacturing costs. To solve this problem, we report our research findings of using low-intensity pulsed ultrasound (LIPUS) to enhance mAb production. LIPUS with frequency of 1.5 MHz and pulse repetition frequency of 1 kHz, as well as duty cycle of 20%, was used to stimulate hybridoma cells to enhance the production of mAb, anti-CD4 (hybridoma GK1.5). The enzyme-linked immunosorbent assay results show a 60.42 ± 7.63% increase of mAb expression in hybridoma cells. The evidence of structural changes of the cellular outer membrane in both transmission electron microscopy and scanning electron microscopy images and the more than 20% lactate dehydrogenase release indicates that the increased mAb production is related to the increased cell permeability induced by LIPUS. This value-added ultrasound technology provides a potential cost-effective solution for pharmaceutical companies to manufacture mAb-based drugs. The technology, in turn, can reduce the drug manufacturing costs and decrease health care spending.     

抗CD20单克隆抗体治疗难治性自身免疫性溶血性贫血

本研究初步观察抗CD20单克隆抗体利妥昔（rituximab）用于治疗难治性自身免疫性溶血性贫血（AIHA）的疗效和安全性。对1例用糖皮质激素、脾切除治疗无效的AIHA患者,采用利妥昔单克隆抗体,375mg/m2,每周1次,共4次,观察溶血症状的改变并监测血红蛋白（Hb）水平及其它检验指标,同时观察有无不良反应发生。结果表明,首次治疗后11天乳酸脱氢酶（LDH）、总胆红素（TBIL）、直接胆红素（IBIL）逐渐下降,第45天降至正常范围;首剂治疗25天后Hb水平比治疗之前升高到95-100g/L以上。治疗后已4月余,患者仍处于缓解状态。治疗过程中未发生明显不良反应。结论：抗CD20单克隆抗体利妥昔用于治疗难治性自身免疫性溶血性贫血是有效而且安全的。     

Assessment of an Anti-Alpha-Toxin Monoclonal Antibody for Prevention and Treatment of Staphylococcus aureus-Induced Pneumonia

Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of Staphylococcus aureus. We previously identified a monoclonal antibody (MAb) against AT that reduced disease severity in a mouse dermonecrosis model. Here, we evaluate the activity of an affinity-optimized variant, LC10, in a mouse model of S. aureus pneumonia. Passive immunization with LC10 increased survival and reduced bacterial numbers in the lungs and kidneys of infected mice and showed protection against diverse S. aureus clinical isolates. The lungs of S. aureus-infected mice exhibited bacterial pneumonia, including widespread inflammation, whereas the lungs of mice that received LC10 exhibited minimal inflammation and retained healthy architecture. Consistent with reduced immune cell infiltration, LC10-treated animals had significantly lower (P < 0.05) proinflammatory cytokine and chemokine levels in the bronchoalveolar lavage fluid than did those of the control animals. This reduction in inflammation and damage to the LC10-treated animals resulted in reduced vascular protein leakage and CO₂ levels in the blood. LC10 was also assessed for its therapeutic activity in combination with vancomycin or linezolid. Treatment with a combination of LC10 and vancomycin or linezolid resulted in a significant increase (P < 0.05) in survival relative to the monotherapies and was deemed additive to synergistic by isobologram analysis. Consistent with improved survival, the lungs of animals treated with antibiotic plus LC10 exhibited less inflammatory tissue damage than those that received monotherapy. These data provide insight into the mechanisms of protection provided by AT inhibition and support AT as a promising target for immunoprophylaxis or adjunctive therapy against S. aureus pneumonia.     

邻苯二甲酸单苄酯单克隆抗体的制备

目的制备抗邻苯二甲酸单苄酯(mono-benzyl phthalate,MBzP)的单克隆抗体。方法本实验利用活泼酯法,将邻苯二甲酸单苄酯分别与载体蛋白BSA和OVA偶联,获得完全抗原MBzP-BSA和MBzP-OVA,用MBzP-BSA免疫Balb/c小鼠,制备杂交瘤细胞,利用ELISA方法检测阳性杂交瘤细胞株分泌抗体的效价。结果获得了稳定分泌抗MBzP的细胞株1B9,以该细胞株体内诱生腹水制备腹水型单克隆抗体,纯化后效价为1∶128 000。结论成功制备了抗邻苯二甲酸单苄酯的单克隆抗体。     

他克莫司治疗白癜风的研究进展

2002年开始，Grimes等尝试他克莫司软膏（tacrolimu ointment）治疗白癜风，获得良好效果。他克莫司是一种免疫调节剂（immunomodulator，TIM），属于大环内酯类，主要用于治疗湿疹。他克莫司为非激素类；可以通过抑制钙调磷酸酶而选择性作用于T淋巴细胞。因此，他克莫司治疗白癜风的初步成功，为本病的治疗开辟了一条新的道路，许多学者投身到该项研中，Kostovic更是认为这是白癜风治疗的一个安全有效的选择。综述如下。     

Intrathecal Treatment with the Anti-Phosphorylcholine Monoclonal Antibody TEPC-15 Decreases Neuronal Damage in Experimental Pneumococcal Meningitis

Background: Neuronal injury in pneumococcal meningitis is a consequence of microglial activation and direct toxicity by bacterial products and systemic inflammation. Methods: The treatment effect of the TEPC-15 antibody recognizing teichoic and lipoteichoic acids was investigated in murine microglial cells and in a rabbit model of pneumococcal meningitis. Results: In vitro, the TEPC-15 antibody recognizing teichoic and lipoteichoic acids increased Streptococcus pneumoniae phagocytosis by murine microglial cells. In rabbit ceftriaxone-treated S. pneumoniae meningitis, intracisternal TEPC-15 reduced the density of apoptotic neurons in the hippocampal dentate gyrus (116 ± 70 vs. 221 ± 132/mm(2); p = 0.03). Cerebrospinal fluid inflammatory parameters (protein, lactate, leukocytes, prostaglandins) were not reduced in TEPC-15-treated rabbits. Conclusion: Intracisternal treatment with the TEPC-15 antibody reduced neuronal damage probably by promoting rapid phagocytosis of bacterial products.     

抗人PCIA1单克隆抗体的制备及其生物特征的研究

目的:筛选制备抗人PCIA1的单克隆抗体,鉴定其生物学特征。方法:采用原核表达并纯化的PCIA1蛋白作为抗原,采用杂交瘤技术制备抗人PCIA1单克隆抗体的杂交瘤,用ELISA进行筛选和鉴定其亚类,并用细胞扒片免疫化学方法检测其反应性。结果:获得了32株分泌抗人PCIA1的McAb杂交瘤细胞,McAb-1A4的染色体呈双亲特点,该McAb与多种人肿瘤细胞株和正常肝细胞株有反应。结论:McAb-1A4可用于PCIA1的细胞内定位研究。     

Recent Advances in Monoclonal Antibody Therapies for Multiple Sclerosis

ABSTRACT

Introduction: Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients.

Areas Covered: Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells.

Expert Opinion: Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside.