单克隆抗体药物在乳腺癌治疗中的应用及进展

目的 介绍近年来单抗药物在乳腺癌治疗中的应用及进展.方法 检索国内外相关资料,并进行汇总、分析和综述.结果 乳腺癌的治疗中单抗药物的应用有单克隆抗体导向药物、免疫偶联物、双特异性单克隆抗体药物等多种类型.结论 单抗药物是乳腺癌治疗史上一个重要里程碑,有着广泛的前景.     

抗体药物在肿瘤治疗中的应用与进展

单克隆抗体药物以其特异性高、亲和力强、血清半衰期长等优点在肿瘤治疗领域得到广泛应用。基于母体单克隆抗体而设计的双特异性抗体、抗体片段、抗体药物偶联物等将抗体类药物的开发推至新的高潮。通过对抗体药物在肿瘤治疗领域的应用和最新进展、抗体药物的结构和作用机制进行介绍,并对肿瘤治疗抗体药物上市与临床开发现状进行总结,以期为抗体药物在肿瘤治疗领域的未来发展提供参考。     

单克隆抗体药物治疗自身免疫性疾病研究进展

自身免疫性疾病（AID）是一种可以对自身抗原发生免疫反应从而导致的疾病,给患者带来了极大的痛苦。治疗AID的传统疗法多采用激素或免疫抑制剂等,虽然可以在一定程度上减轻病症,但无法根治,并且长期用药会引起巨大的副作用。近年来,对单克隆抗体的广泛研究,使得单克隆抗体药物成为治疗AID的首要选择。单克隆抗体通过不同的作用机制,作用于不同的靶点,靶向性引起自身免疫应答治疗各种自身免疫性疾病,并且随着对单克隆抗体不断地深入研究,越来越多的全人源性单克隆抗体药物的上市应用,将单克隆抗体治疗AID推向新的起点。本研究就单克隆抗体药物治疗五种AID的研究进展做一综述。     

抗肿瘤抗生素和单克隆抗体药物的研究进展

微生物产物是发现与研制新药的丰富资源，近年来，报道了作用于各种不同靶点的抗肿瘤抗生素，单克隆抗体（单抗）对相应的抗原具有高度特异性，可以针对特定的分子靶点，制备与之特异性结合的单抗，在肿瘤治疗中有巨大的潜力，Mylotarg是由单抗和抗肿瘤抗生素calicheamicin连接的偶联物，它的研制成功表现，抗肿瘤抗生素与单抗药物研究出现了新的结合点，利用特定的抗肿瘤抗生素作为“弹头” 物质，分别与不同的单抗进行连接，将可构建一系列的，针对各种癌症的抗肿瘤单抗药物。     

单克隆抗体药物及抗体偶联药物的药代动力学研究进展

近几年来,随着国际上一些重磅生物药专利的到期或即将到期,以及以PD-1、PD-L1等免疫检查点为靶标的单克隆抗体药物的上市和其在肿瘤治疗方面显示的疗效,在国内引发了抗体药物的仿制以及研发热潮。与传统小分子药物的药代动力学特征不同,抗体类药物的药物代谢动力学特征有着其特有的规律。本文从药代动力学特征的四个方面：吸收（Absorption）、分布（Distribution）、代谢（Metabolism）、排泄（Excretion）,对单克隆抗体药物以及抗体偶联药物（Antibody-Drug Conjugates, ADC）的药代动力学特征进行综述。     

抗体偶联药物的研发进展和挑战

抗体偶联药物（ADC）由单克隆抗体与不同数目的小分子毒素通过连接子偶联组成,是近年来肿瘤学发展较快的药物类别之一。由于兼具单抗药物的高靶向性以及细胞毒素在肿瘤组织中高活性的双重优点,ADC药物可高效杀伤肿瘤细胞,较化疗药物不良反应更低,较传统抗体类肿瘤药物具有更好的疗效,是近年来肿瘤创新药研发的热点。随着新一代工程抗体展现出良好的治疗前景以及新药研发技术的不断突破,抗体偶联药物经历了三个发展阶段,技术日臻成熟,但ADC药物还存在诸多问题和挑战。本文主要从抗体偶联药物的研发历程、抗体、连接子、偶联技术及细胞毒素的类型等方面进行综述,为ADC创新药物研发提供参考。     

抗肿瘤抗体药物研究进展

自1997年以来,抗体药物用于肿瘤治疗取得突破性的进展。据统计,国内外已有约17种抗体药物被批准用于临床肿瘤治疗。除了一直比较成功的裸抗体,抗体药物偶联物(ADC)成为抗肿瘤抗体药物研发的新热点。抗原靶标及作用机制特点决定了抗肿瘤抗体药物在临床的安全性和疗效。本文主要从肿瘤细胞杀伤机制、作为抗体靶标的肿瘤抗原、在临床的应用情况及ADC纳米粒研究方面对抗肿瘤抗体药物进行了综述。     

单克隆抗体作战血液系统恶性肿瘤

近年来,多个用于治疗血液系统恶性肿瘤的单克隆抗体相继获得FDA批准上市,本文系统而全面地介绍了单克隆抗体的命名和分类、非结合单抗的研究进展以及偶联单抗(包括单抗偶联物、放射标记单抗和靶向抗体-酶复合物)的作用机制和临床研究。为您展示了国外在单克隆抗体治疗血液系统肿瘤方面的最新动态和发展方向。     

双特异性单克隆抗体在肿瘤治疗方面的…

双特异性单克隆抗体（ＢｓＭｃＡｂ）可介导肿瘤效应物至肿瘤部位、杂交－杂交瘤ＢｓＭｃＡｂ可克服化学交联法对抗体和药物的损害，并且性质稳定、不易脱落、还有浓集效应，并可诱导、增强细胞毒细胞的杀伤性，导向作用和治疗作用强，副作用较小，是肿瘤导向治疗的新方法。     

肿瘤靶向药物抗体-药物偶联物的研究进展

抗体-药物偶联物(Antibody-drug conjugates,ADC)具有单克隆抗体的靶向特异性和细胞毒素的抗肿瘤能力,其利用化学接头将细胞毒性药物与单克隆抗体偶联,与肿瘤部位的靶抗原结合后释放毒素.尽管概念简单,但是结构设计复杂、药物副作用明显和疗效欠佳等问题为其进一步研究应用带来了挑战.随着新技术的出现,AD...     

Development and Evaluation of Monoclonal Antibodies for Paxilline

Paxilline (PAX) is a tremorgenic mycotoxin that has been found in perennial ryegrass infected with Acremonium lolii. To facilitate screening for this toxin, four murine monoclonal antibodies (mAbs) were developed. In competitive indirect enzyme-linked immunosorbent assays (CI-ELISAs) the concentrations of PAX required to inhibit signal development by 50% (IC₅₀s) ranged from 1.2 to 2.5 ng/mL. One mAb (2-9) was applied to the detection of PAX in maize silage. The assay was sensitive to the effects of solvents, with 5% acetonitrile or 20% methanol causing a two-fold or greater increase in IC₅₀. For analysis of silage samples, extracts were cleaned up by adsorbing potential matrix interferences onto a solid phase extraction column. The non-retained extract was then diluted with buffer to reduce solvent content prior to assay. Using this method, the limit of detection for PAX in dried silage was 15 µg/kg and the limit of quantification was 90 µg/kg. Recovery from samples spiked over the range of 100 to 1000 µg/kg averaged 106% ± 18%. The assay was applied to 86 maize silage samples, with many having detectable, but none having quantifiable, levels of PAX. The results suggest the CI-ELISA can be applied as a sensitive technique for the screening of PAX in maize silage.     

抗红花花粉蛋白单克隆抗体的研制

目的：研究红花中过敏原性物质的检测和评价方法,为筛查红花制剂过敏原残留、优化红花制剂工艺、预防红花制剂过敏反应的发生提供新的研究思路和方法。方法：以水煮醇沉法提取红花花粉蛋白,用花粉蛋白免疫小鼠,筛选特异性细胞克隆,扩增、纯化制备抗红花蛋白单克隆抗体。采用酶联免疫吸附剂测定（ELISA）方法检测单克隆抗体对红花抗原的特异性识别情况。结果：3株单克隆抗体均能特异性识别红花抗原。结论：抗红花蛋白单克隆抗体对研究红花过敏反应的发生机理、优化红花制剂工艺及降低过敏反应发生具有重要意义。     

Application of Quantitative Pharmacology in Development of Therapeutic Monoclonal Antibodies

The advancement of therapeutic monoclonal antibodies during various stages of the drug development process can be effectively streamlined when appropriate translational strategies are applied. Design of successful translational strategies for development of monoclonal antibodies should allow for understanding of the dose– and concentration–response relationships with respect to both beneficial and toxic effects from early phases of drug development. Evaluation of relevant biomarkers during early stages of drug development should facilitate the successful design of safe and effective dosing strategies. Moreover, application of quantitative pharmacology is critical for translation of exposure–response relationships early on.     

Monoclonal Antibodies in Hapten Immunoassays

This review deals with the potency of monoclonal antibodies (MAbs) to haptens in immunoassays. Specificity and affinity of MAbs to haptens are the major determinants to be considered. Specificity of MAbs depends on the selection of the hapten coupling site to the carrier protein and the antigen used for the screening of MAbs. Nevertheless, cross-reactivity can occur with compounds related to the hapten. This poly specificity may be circumvented with the use of many MAbs, as has been demonstrated for MAbs to cyclosporine. Affinity of MAbs to haptens is often lower than that of corresponding polyclonal antibodies (PAbs), thereby limiting assay sensitivity. Low affinity is more frequently observed with low molecular weight (100–300) haptens than with larger haptens, such as digoxin or cyclosporine. Affinity enhancement by increasing resemblance to the immunogen can be effective in resolving the lack of sensitivity. With suitable selection strategies, MAbs exhibit real advantages over classical PAbs to haptens because large amounts of worldwide standardized reagents can be prepared.     

Monoclonal Antibodies as Magic Bullets

Monoclonal antibodies have been used as experimental therapy in humans since the beginning of the 1980s (A. N. Houghton and D. A. Scheinberg. Semin. Oncol. 13:165–179, 1986). They have been hailed as the prototypical magic bullet drug because of their inherent capacity for specificity. Consequently, monoclonal antibodies have many possible therapeutic applications with varied potential for successful outcome. Current review articles discussing monoclonal antibody therapy deal with the application of monoclonal antibodies within specific areas of medicine. The aim of this review is to summarize the current reviews and provide a broader perspective on the medical applications of monoclonal antibodies along with some general principles by which their therapeutic success or failure might be understood.     

Therapeutic Applications of Anti-TNF Monoclonal Antibodies

Tumour necrosis factor α (TNF) is a major product of activated macrophages which has a wide range of biological actions that have been implicated in a rumber of human diseases. This review presents the evidence that has been generated in animal models which suggests that TNF plays an important role in the pathology of septic shock, rheumatoid arthritis and inflammatory bowel diseases (Crohn's disease and ulcerative colitis). Anti-TNF antibodies either reduce or block the onset of symptoms in these models which suggests that this class of antibody may have useful therapeutic effects. Recent results of human clinical trials with a mouse antibody, BAYX 1351, and two recombinant antibodies, cA2 and CDP571, are discussed which indicate that the promising results in animals may be duplicated in man.     

单抗类药物的免疫原性问题及其控制

单抗类药物(单克隆抗体药物和受体-Fc融合蛋白药物)近年来在癌症和自身免疫性疾病等领域取得了显著的疗效。根据诱发的抗药物抗体的类型不同,单抗类药物的免疫原性可能导致不同的临床后果,直至影响单抗类药物的有效性和安全性。单抗类药物免疫原性的发生机制尚没有明确的定论,可能与多种因素有关,其中蛋白质多聚体对免疫原性有显著影响。根据"质量源于设计"的原则,从单抗类药物的分子设计和工艺设计出发,采取人源化改造、开发人类抗体、检测和控制产品中多聚体含量等,有助于降低单抗类药物的免疫原性,实现单抗类药物的有效性、安全性和可生产性之间的平衡。