共查询到18条相似文献,搜索用时 93 毫秒
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双特异性抗体(BsAb)是改造抗体治疗效果的发展方向之一,现已成为抗体工程研究领域的热点。在过去20年的研究中.研究人员看到了常规BsAb的潜能以及它的不足。随着分子生物学技术的迅速发展,出现了利用基因工程手段构建的BsAb的多种模式,并且有多种BsAb制剂已经用于肿瘤的初期临床诊断和治疗。该文对BsAb最新的研究进展和肿瘤治疗中的应用进行了阐述。 相似文献
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双特异性单克隆抗体(Bispecific mono-clonal antibody,BSAb)是已发展起来的免疫治 疗和细胞生物学基础研究的新课题。它是两亲代单克隆抗体(Mab)的杂交抗体,同时具备了两亲代抗体的特异性,因此可与两种不同的抗原分子结合,显示了功能上的单价性。1983年Milstein和Cuello第一次利用两次杂交瘤技 相似文献
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T细胞重定向双特异性抗体能同时结合肿瘤相关抗原和T细胞表面CD3分子,通过将T细胞与肿瘤细胞桥联而激活T细胞发挥抗肿瘤作用,是肿瘤免疫治疗中极具潜力的策略之一。该疗法已成功应用于多种血液肿瘤的治疗,但在实体瘤治疗领域进展缓慢。就近年T细胞重定向双特异性抗体在肿瘤治疗方面所面临的主要挑战及解决策略进行综述,以探讨未来有可能改善其疗效的潜在策略。 相似文献
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BiTEs(bispecificTcellengagers)是一种以T细胞作为效应细胞的双特异性单链抗体 ,它具有两个抗原结合臂 ,可以同时和T细胞及靶细胞结合 ,并激活细胞毒性T细胞杀伤病变细胞。和其它双特异性抗体相比 ,BiTEs的分子柔韧性更好 ,能更好地促进CD3复合体和肿瘤靶标的连接 ,并且它不受T细胞受体和靶细胞上MHCⅠ类分子的约束 ,不需要共刺激分子的参与 ,是一种极具应用潜力的抗体形式。就BiTEs的结构、作用机理及其在肿瘤临床上的应用前景几个方面做一综述。 相似文献
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从纳米抗体的研究进展,双特异性纳米抗体在感染类疾病、肿瘤以及免疫系统疾病治疗领域的研究成果、研究热点及发展前景等方面综述了双特异性纳米抗体的研究进展并分析了未来可能的发展方向.首先比较了纳米抗体与全长单克隆抗体之间的差异并阐述了双特异性纳米抗体具备的独特优势;继而概括了双特异性纳米抗体的发展历程,并对新冠病毒的中和性抗... 相似文献
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双特异性抗体(bispecific antibody,BsAb)是一类具有两种不同抗原结合臂的抗体,由两个不同的轻链和重链组成,可同时结合两种不同的抗原.自20世纪60年代双特异性抗体的概念被Nisonoff等首次提出以后,由于其独特的结构特异性和显著的肿瘤治疗效果,双特异性抗体迅速成为免疫治疗领域的热门研究项目.近些... 相似文献
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高新 《国外医学:分子生物学分册》1998,20(3):133-136
双价、双特异性单链抗体是最近几年才出现的一类新的基因工程抗体分子,它在临床诊断和治疗上有着广泛的应用前景,尤其是在肿瘤和病毒的诊治方面更具突出优势。本对其性质,制备方法及应用前景作了系统的综述。 相似文献
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Diane L Rossi Edmund A Rossi Thomas M Cardillo David M Goldenberg Chien-Hsing Chang 《MABS-AUSTIN》2014,6(2):381-391
Various constructs of bispecific antibodies (bsAbs) to redirect effector T cells for the targeted killing of tumor cells have shown considerable promise in both preclinical and clinical studies. The single-chain variable fragment (scFv)-based formats, including bispecific T-cell engager (BiTE) and dual-affinity re-targeting (DART), which provide monovalent binding to both CD3 on T cells and to the target antigen on tumor cells, can exhibit rapid blood clearance and neurological toxicity due to their small size (~55 kDa). Herein, we describe the generation, by the modular DOCK-AND-LOCKTM (DNLTM) method, of novel T-cell redirecting bispecific antibodies, each comprising a monovalent anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. The potential advantages of this design include bivalent binding to tumor cells, a larger size (~130 kDa) to preclude renal clearance and penetration of the blood-brain barrier, and potent T-cell mediated cytotoxicity. These prototypes were purified to near homogeneity, and representative constructs were shown to provoke the formation of immunological synapses between T cells and their target tumor cells in vitro, resulting in T-cell activation and proliferation, as well as potent T-cell mediated anti-tumor activity. In addition, in vivo studies in NOD/SCID mice bearing Raji Burkitt lymphoma or Capan-1 pancreatic carcinoma indicated statistically significant inhibition of tumor growth compared with untreated controls. 相似文献
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《MABS-AUSTIN》2013,5(2):381-391
Various constructs of bispecific antibodies (bsAbs) to redirect effector T cells for the targeted killing of tumor cells have shown considerable promise in both preclinical and clinical studies. The single-chain variable fragment (scFv)-based formats, including bispecific T-cell engager (BiTE) and dual-affinity re-targeting (DART), which provide monovalent binding to both CD3 on T cells and to the target antigen on tumor cells, can exhibit rapid blood clearance and neurological toxicity due to their small size (~55 kDa). Herein, we describe the generation, by the modular DOCK-AND-LOCKTM (DNLTM) method, of novel T-cell redirecting bispecific antibodies, each comprising a monovalent anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. The potential advantages of this design include bivalent binding to tumor cells, a larger size (~130 kDa) to preclude renal clearance and penetration of the blood-brain barrier, and potent T-cell mediated cytotoxicity. These prototypes were purified to near homogeneity, and representative constructs were shown to provoke the formation of immunological synapses between T cells and their target tumor cells in vitro, resulting in T-cell activation and proliferation, as well as potent T-cell mediated anti-tumor activity. In addition, in vivo studies in NOD/SCID mice bearing Raji Burkitt lymphoma or Capan-1 pancreatic carcinoma indicated statistically significant inhibition of tumor growth compared with untreated controls. 相似文献
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Sanket Patke Ji Li Peiyin Wang Dion Slaga Jennifer Johnston Sunil Bhakta 《MABS-AUSTIN》2017,9(3):430-437
Bispecific antibodies are a growing class of therapeutic molecules. Many of the current bispecific formats require DNA engineering to convert the parental monoclonal antibodies into the final bispecific molecules. We describe here a method to generate bispecific molecules from hybridoma IgGs in 3–4 d using chemical conjugation of antigen-binding fragments (Fabs) (bisFabs). Proteolytic digestion conditions for each IgG isotype were analyzed to optimize the yield and quality of the final conjugates. The resulting bisFabs showed no significant amounts of homodimers or aggregates. The predictive value of murine bisFabs was tested by comparing the T-cell redirected cytotoxic activity of a panel of antibodies in either the bisFab or full-length IgG formats. A variety of antigens with different structures and expression levels was used to extend the comparison to a wide range of binding geometries and antigen densities. The activity observed for different murine bisFabs correlated with those observed for the full-length IgG format across multiple different antigen targets, supporting the use of bisFabs as a screening tool. Our method may also be used for the screening of bispecific antibodies with other mechanisms of action, allowing for a more rapid selection of lead therapeutic candidates. 相似文献
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《MABS-AUSTIN》2013,5(2):182-197
Monoclonal antibodies are widely used for the treatment of cancer, inflammatory and infectious diseases and other disorders. Most of the marketed antibodies are monospecific and therefore capable of interacting and interfering with a single target. However, complex diseases are often multifactorial in nature, and involve redundant or synergistic action of disease mediators or upregulation of different receptors, including crosstalk between their signaling networks. Consequently, blockade of multiple, different pathological factors and pathways may result in improved therapeutic efficacy. This result can be achieved by combining different drugs, or use of the dual targeting strategies applying bispecific antibodies that have emerged as an alternative to combination therapy. This review discusses the various dual targeting strategies for which bispecific antibodies have been developed and provides an overview of the established bispecific antibody formats. 相似文献
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A process was developed for large‐scale assembly of IgG1 and IgG4 bispecific antibodies from knob and hole half‐antibodies. We optimized assembly conditions such as pH, temperature, stabilizers, and reducing agent. We also identified and exploited structural changes unique to knob and hole half‐antibodies with the result of improving assembly outcome, specifically storing half‐antibodies at higher pH will condition them to assemble more rapidly and produce fewer high molecular‐weight species (HMWS). Application of heat to the assemblies resulted in an acceleration of assembly rate, with optimal formation of bispecific achieved at 37°C. IgG4 half‐antibodies were unusually sensitive to temperature‐dependent formation of HMWS in pre‐assembly conditioning as well as during assembly. We selected l ‐histidine and Polyvinylpyrrolidone (PVP) as stabilizers to prevent HMWS formation in IgG4, and achieved rapid and high‐efficiency assemblies. Using optimized assembly conditions, we developed and scaled up a method for assembling bispecific antibody with 90% assembly efficiency over 6 h with minimal impact to product quality, generating a pool with bispecific antibody for downstream processing. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1315–1322, 2015 相似文献
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《MABS-AUSTIN》2013,5(6):775-783
Bispecific antibodies are proteins that bind two different antigens and may retarget immune cells with a binding moiety specific for a leukocyte marker. A binding event in blood could in principle prevent antibody extravasation and accumulation at the site of disease. In this study, we produced and characterized two tetravalent bispecific antibodies that bind with high affinity to the alternatively-spliced EDB domain of fibronectin, a tumor-associated antigen. The bispecific antibodies simultaneously engaged the cognate antigens (murine T cell co-receptor CD3 and hen egg lysozyme) and selectively accumulated on murine tumors in vivo. The results, which were in agreement with predictions based on pharmacokinetic modeling and antibody binding characteristics, confirmed that bispecific antibodies can reach abluminal targets without being blocked by peripheral blood leukocytes. 相似文献