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The role of TRIM59 in immunity and immune-related diseases. TRIM59 在免疫和免疫相关疾病中的作用。
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2022-08-17 DOI: 10.1080/08830185.2022.2102618
Zheng Jin, Tiffany Chen, Zhenhua Zhu, Baohui Xu, Dongmei Yan

TRIM59 is a member of the tripartite motif containing (TRIM) protein family. It functions as an E3 ubiquitin ligase through its RING domain and is expressed by multiple types of cells. Physiogically, TRIM59 is involved in development, immune response, and the invasion and metastasis of tumors. In this review, we first describe the structure, expression, and subcellular location of TRIM59. Then, we summarize emerging evidence for TRIM59 in immunological diseases including infection, vascular diseases, autoimmunity, and tumor immunity. Additionally, we discuss important molecular signaling pathways that mediate TRIM59 activity. Altogether, the accumulating evidence suggests that manipulating TRIM59 levels and activity may open an avenue for innovative therapies for immune diseases and tumors.

TRIM59 是含三方基序(TRIM)蛋白家族的成员。它通过其 RING 结构域发挥 E3 泛素连接酶的功能,可在多种类型的细胞中表达。在生理上,TRIM59 参与发育、免疫反应以及肿瘤的侵袭和转移。在这篇综述中,我们首先描述了 TRIM59 的结构、表达和亚细胞位置。然后,我们总结了 TRIM59 在免疫疾病(包括感染、血管疾病、自身免疫和肿瘤免疫)中的新证据。此外,我们还讨论了介导 TRIM59 活性的重要分子信号通路。总之,不断积累的证据表明,操纵 TRIM59 的水平和活性可能为免疫疾病和肿瘤的创新疗法开辟一条途径。
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引用次数: 1
Exploring the role of neutrophils in infectious and noninfectious pulmonary disorders. 探索中性粒细胞在感染性和非感染性肺部疾病中的作用。
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2023-06-24 DOI: 10.1080/08830185.2023.2222769
Alisha Arora, Archana Singh

With the change in global environment, respiratory disorders are becoming more threatening to the health of people all over the world. These diseases are closely linked to performance of immune system. Within the innate arm of immune system, Neutrophils are an important moiety to serve as an immune defense barrier. They are one of the first cells recruited to the site of infection and plays a critical role in pathogenesis of various pulmonary diseases. It is established that the migration and activation of neutrophils can lead to inflammation either directly or indirectly and this inflammation caused is very crucial for the clearance of pathogens and resolution of infection. However, the immunopathological mechanisms involved to carry out the same is very complex and not well understood. Despite there being studies concentrating on the role of neutrophils in multiple respiratory diseases, there is still a long way to go in order to completely understand the complexity of the participation of neutrophils and mechanisms involved in the development of these respiratory diseases. In the present article, we have reviewed the literature to comprehensively provide an insight in the current development and advancements about the role of neutrophils in infectious respiratory disorders including viral respiratory disorders such as Coronavirus disease (COVID-19) and bacterial pulmonary disorders with a focused review on pulmonary tuberculosis as well as in noninfectious disorders like Chronic obstructive pulmonary disease (COPD) and asthma. Also, future directions into research and therapeutic targets have been discussed for further exploration.

随着全球环境的变化,呼吸系统疾病正日益威胁着全世界人民的健康。这些疾病与免疫系统的表现密切相关。在先天性免疫系统中,中性粒细胞是一道重要的免疫防御屏障。它们是最先被招募到感染部位的细胞之一,在各种肺部疾病的发病机制中起着至关重要的作用。中性粒细胞的迁移和活化可直接或间接导致炎症,而这种炎症对清除病原体和解决感染至关重要。然而,实现这一目标所涉及的免疫病理机制非常复杂,人们对其了解不多。尽管有研究集中探讨了中性粒细胞在多种呼吸系统疾病中的作用,但要完全了解中性粒细胞参与这些呼吸系统疾病的复杂性及其发病机制,还有很长的路要走。在本文中,我们回顾了相关文献,全面介绍了中性粒细胞在感染性呼吸系统疾病(包括冠状病毒病(COVID-19)等病毒性呼吸系统疾病和肺结核等细菌性肺部疾病)以及慢性阻塞性肺疾病(COPD)和哮喘等非感染性疾病中的作用的最新进展。此外,还讨论了未来的研究方向和治疗目标,以供进一步探讨。
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引用次数: 1
Immunological and biological dissection of normal and tumoral salivary glands. 正常和肿瘤唾液腺的免疫学和生物学解剖。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 DOI: 10.1080/08830185.2021.1958806
Mohammad Reza Haghshenas, Hamid Ghaderi, Hossein Daneste, Abbas Ghaderi

Salivary glands naturally play central roles in oral immunity. The salivary glands microenvironment inevitable may be exposed to exogenous factors consequently triggering the initiation and formation of various malignant and benign tumors. Mesenchymal stem cells are recruited into salivary gland microenvironment, interact with tumor cells, and induce inhibitory cytokines as well as cells with immunosuppressive phenotypes such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). The immune components and tumor immune responses in malignant and benign SGTs are still under investigation. Immune responses may directly play a limiting role in tumor growth and expansion, or may participate in formation of a rich milieu for tumor growth in cooperation with other cellular and regulatory molecules. Immune checkpoint molecules (e.g. PDLs, HLA-G and LAG3) are frequently expressed on tumor cells and/or tumor-infiltrating lymphocytes (TILs) in salivary gland microenvironment, and an increase in their expression is associated with T cell exhaustion, immune tolerance and tumor immune escape. Chemokines and chemokine receptors have influential roles on aggressive behaviors of SGTs, and thereby they could be candidate targets for cancer immunotherapy. To present a broad knowledge on salivary glands, this review first provides a brief description on immunological functions of normal salivary glands, and then describe the SGT's tumor microenvironment, by focusing on mesenchymal stem cells, immune cell subsets, immune checkpoint molecules, chemokines and chemokine receptors, and finally introduces immune checkpoint inhibitors as well as potential targets for cancer therapy.

唾液腺在口腔免疫中自然发挥着核心作用。唾液腺微环境不可避免地会受到外源因素的影响,从而触发各种恶性和良性肿瘤的发生和形成。间充质干细胞被招募到唾液腺微环境中,与肿瘤细胞相互作用,并诱导抑制性细胞因子以及具有免疫抑制表型的细胞,如髓源性抑制细胞(MDSCs)和调节性T细胞(Tregs)。恶性和良性sgt的免疫成分和肿瘤免疫反应仍在研究中。免疫反应可能直接限制肿瘤的生长和扩张,或者与其他细胞和调节分子合作参与肿瘤生长的丰富环境的形成。免疫检查点分子(如pdl、HLA-G和LAG3)经常在唾液腺微环境的肿瘤细胞和/或肿瘤浸润淋巴细胞(til)上表达,其表达增加与T细胞耗竭、免疫耐受和肿瘤免疫逃逸有关。趋化因子和趋化因子受体对sgt的攻击行为有影响,因此它们可能是癌症免疫治疗的候选靶点。为了广泛地了解唾液腺,本文首先对正常唾液腺的免疫功能进行了简要的介绍,然后从间充质干细胞、免疫细胞亚群、免疫检查点分子、趋化因子和趋化因子受体等方面对SGT的肿瘤微环境进行了描述,最后介绍了免疫检查点抑制剂以及癌症治疗的潜在靶点。
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引用次数: 2
The role of γδ T cells in the interaction between commensal and pathogenic bacteria in the intestinal mucosa. γδ T细胞在肠粘膜共生菌和致病菌相互作用中的作用。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 Epub Date: 2022-05-18 DOI: 10.1080/08830185.2022.2076846
Xiaoxiao Wu, Bing Gu, Huan Yang

The intestinal mucosa is an important structure involved in resistance to pathogen infection. It is mainly composed of four barriers, which have different but interrelated functions. Pathogenic bacteria can damage these intestinal mucosal barriers. Here, we mainly review the mechanisms of pathogen damage to biological barriers. Most γδ T cells are located on the surface of the intestinal mucosa, with the ability to migrate and engage in crosstalk with microorganisms. Commensal bacteria are involved in the activation and migration of γδ T cells to monitor the invasion of pathogens. Pathogen invasion alters the migration pattern of γδ T cells. γδ T cells accelerate pathogen clearance and limit opportunistic invasion of commensal bacteria. By discussing these interactions among γδ T cells, commensal bacteria and pathogenic bacteria, we suggest that γδ T cells may link the interactions between commensal bacteria and pathogenic bacteria.

肠黏膜是抵抗病原体感染的重要结构。它主要由四个屏障组成,它们具有不同但相互关联的功能。病原菌会破坏这些肠黏膜屏障。在这里,我们主要综述病原体对生物屏障的破坏机制。大多数γδT细胞位于肠粘膜表面,具有迁移能力并与微生物发生串扰。共生细菌参与γδT细胞的激活和迁移,以监测病原体的入侵。病原体入侵改变了γδT细胞的迁移模式。γδT细胞加速病原体清除并限制共生细菌的机会性入侵。通过讨论γδT细胞、共生菌和致病菌之间的这些相互作用,我们认为γδT淋巴细胞可能将共生菌和致病菌之间的相互作用联系起来。
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引用次数: 2
Role of thymus in health and disease. 胸腺在健康和疾病中的作用。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 DOI: 10.1080/08830185.2022.2064461
Surendra Gulla, Madhava C Reddy, Vajra C Reddy, Sriram Chitta, Manjula Bhanoori, Dakshayani Lomada

The thymus is a primary lymphoid organ, essential for the development of T-cells that will protect from invading pathogens, immune disorders, and cancer. The thymus decreases in size and cellularity with age referred to as thymus involution or atrophy. This involution causes decreased T-cell development and decreased naive T-cell emigration to the periphery, increased proportion of memory T cells, and a restricted, altered T-cell receptor (TCR) repertoire. The changes in composition and function of the circulating T cell pool as a result of thymic involution led to increased susceptibility to infectious diseases including the recent COVID and a higher risk for autoimmune disorders and cancers. Thymic involution consisting of both structural and functional loss of the thymus has a deleterious effect on T cell development, T cell selection, and tolerance. The mechanisms which act on the structural (cortex and medulla) matrix of the thymus, the gradual accumulation of genetic mutations, and altered gene expressions may lead to immunosenescence as a result of thymus involution. Understanding the molecular mechanisms behind thymic involution is critical for identifying diagnostic biomarkers and targets for treatment help to develop strategies to mitigate thymic involution-associated complications. This review is focused on the consequences of thymic involution in infections, immune disorders, and diseases, identifying potential checkpoints and potential approaches to sustain or restore the function of the thymus particularly in elderly and immune-compromised individuals.

胸腺是一个初级淋巴器官,对t细胞的发育至关重要,t细胞可以保护人体免受入侵病原体、免疫紊乱和癌症的侵袭。胸腺的大小和细胞数量随着年龄的增长而减少,称为胸腺退化或萎缩。这种内化导致T细胞发育减少,初始T细胞向外周迁移减少,记忆T细胞比例增加,T细胞受体(TCR)库受限改变。胸腺内翻导致循环T细胞池组成和功能的变化,导致对传染病的易感性增加,包括最近的COVID,以及自身免疫性疾病和癌症的风险增加。胸腺内化包括胸腺结构和功能的丧失,对T细胞的发育、T细胞的选择和耐受性有有害的影响。作用于胸腺结构(皮层和髓质)基质的机制、基因突变的逐渐积累和基因表达的改变可能导致胸腺退化导致免疫衰老。了解胸腺复旧背后的分子机制对于确定诊断性生物标志物和治疗靶点至关重要,有助于制定减轻胸腺复旧相关并发症的策略。这篇综述的重点是胸腺退化在感染、免疫紊乱和疾病中的后果,确定潜在的检查点和潜在的方法来维持或恢复胸腺功能,特别是在老年人和免疫功能低下的个体中。
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引用次数: 4
Pathophysiological functions of self-derived DNA. 自源DNA的病理生理功能。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 DOI: 10.1080/08830185.2022.2070616
Daisuke Ori, Taro Kawai

Inflammation plays indispensable roles in building the immune responses such as acquired immunity against harmful pathogens. Furthermore, it is essential for maintaining biological homeostasis in ever-changing conditions. Pattern-recognition receptors (PRRs) reside in cell membranes, endosomes or cytoplasm, and function as triggers for inflammatory responses. Binding of pathogen- or self-derived components, such as DNA, to PRRs activates downstream signaling cascades, resulting in the production of a series of pro-inflammatory cytokines and type I interferons (IFNs). While these series of responses are essential for host defense, the unexpected release of DNA from the nucleus or mitochondria of host cells can lead to autoimmune and autoinflammatory diseases. In this review, we focus on DNA-sensing mechanisms via PRRs and the disorders and extraordinary conditions caused by self-derived DNA.

炎症在建立免疫反应中起着不可或缺的作用,例如对有害病原体的获得性免疫。此外,它是在不断变化的条件下维持生物稳态所必需的。模式识别受体(PRRs)存在于细胞膜、内体或细胞质中,是炎症反应的触发因子。病原体或自身衍生成分(如DNA)与PRRs结合,激活下游信号级联反应,导致一系列促炎细胞因子和I型干扰素(ifn)的产生。虽然这一系列反应对宿主防御至关重要,但从宿主细胞的细胞核或线粒体中意外释放DNA可导致自身免疫和自身炎症疾病。在这篇综述中,我们重点介绍了通过PRRs的DNA传感机制以及由自源性DNA引起的疾病和异常情况。
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引用次数: 0
FAM26F: An Enigmatic Protein Having a Complex Role in the Immune System. FAM26F:一种在免疫系统中具有复杂作用的神秘蛋白。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 DOI: 10.1080/08830185.2016.1206098
Uzma Malik, Aneela Javed

Mammalian immune system is a complex amalgam of diverse cellular and noncellular components such as cytokines, receptors and co-receptors. FAM26F (family with sequence similarity 26, member F) is a recently identified tetraspanin-like membrane glycoprotein which is predicted to make homophilic interactions and potential synapses between several immune cells including CD4+, CD8+, NK, dendritic cells and macrophages. Various whole transcriptome analyses have demonstrated the differential expression of FAM26F in several bacterial, viral and parasitic infections, in certain pathophysiological conditions such as liver and heart transplantation, and in various cancers. The complete understanding of transcriptional regulation of FAM26F is in its infancy however it is up regulated by various stimulants such as polyI:C, LPS, INF gamma and TNF alpha, and via various proposed pathways including TLR3, TLR4 IFN-β and Dectin-1. These pathways can merge in STAT1 activation. The synergistic expression of FAM26F on both NK-cells and myeloid dendritic cells is required to activate NK-cells against tumors via its cytoplasmic tail, thus emphasizing therapeutic potential of FAM26F for NK sensitive tumors. Current review provides a comprehensive basis to propose that FAM26F expression level is at least a hallmark for IFN-γ-lead immune responses and thus can proficiently be regarded as an early diagnostic marker. Future investigation dissecting the role of FAM26F in activation of various immune cell populations in local amplification by cell-cell contact is crucial to provide the missing link imperative for elucidating the relevance of this protein in immune responses.

哺乳动物的免疫系统是一个由细胞因子、受体和共受体等多种细胞和非细胞成分组成的复杂混合体。FAM26F (family with sequence similarity 26, member F)是最近发现的一种类似四联蛋白(tetraspanin-like)的膜糖蛋白,可在多种免疫细胞(包括CD4+、CD8+、NK、树突状细胞和巨噬细胞)之间产生亲同质相互作用和潜在突触。各种全转录组分析已经证明FAM26F在几种细菌、病毒和寄生虫感染、某些病理生理条件(如肝脏和心脏移植)以及各种癌症中的差异表达。对FAM26F转录调控的全面了解尚处于起步阶段,但它受到多种刺激物的上调,如polyI:C、LPS、INF γ和TNF α,并通过各种被提出的途径,包括TLR3、TLR4、IFN-β和Dectin-1。这些通路可以在STAT1激活中合并。FAM26F在NK细胞和髓系树突状细胞上的协同表达是激活NK细胞抗肿瘤的必要条件,从而强调了FAM26F对NK敏感肿瘤的治疗潜力。目前的综述提供了全面的基础,提出FAM26F表达水平至少是IFN-γ-铅免疫反应的标志,因此可以熟练地视为早期诊断标志物。未来的研究剖析FAM26F在细胞与细胞接触的局部扩增中激活各种免疫细胞群中的作用,对于阐明该蛋白在免疫应答中的相关性至关重要。
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引用次数: 6
Diversity of T cells in the skin: Novel insights. 皮肤中T细胞的多样性:新的见解。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 DOI: 10.1080/08830185.2021.1985116
Natalija Novak, Leticia Tordesillas, Beatriz Cabanillas

T cells populate the skin to provide an effective immunosurveillance against external insults and to maintain tissue homeostasis. Most cutaneous T cells are αβ T cells, however, γδ T cells also exist although in much lower frequency. Different subsets of αβ T cells can be found in the skin, such as short-lived effector T cells, central memory T cells, effector memory T cells, and tissue-resident memory T cells. Their differential biology, function, and location provide an ample spectrum of immune responses in the skin. Foxp3+ memory regulatory T cells have a pivotal role in maintaining homeostasis in the skin and their dysregulation has been linked with different skin pathologies. The skin also contains populations of non-classical T cells, such as γδ T cells, NK T cells, and MR1-restricted T cells. Their role in skin homeostasis and response to pathogens has been well established in the past years, however, there is also growing evidence of their role in mediating allergic skin inflammation and promoting sensitization to allergens. In this review, we provide an updated overview on the different subsets of T cells that populate the skin with a specific focus on their role in allergic skin inflammation.

T细胞聚集在皮肤上,提供有效的免疫监视,抵抗外界的伤害,并维持组织的稳态。大多数皮肤T细胞是αβ T细胞,然而,γδ T细胞也存在,尽管频率低得多。在皮肤中可以发现不同的αβ T细胞亚群,如短命效应T细胞、中枢记忆T细胞、效应记忆T细胞和组织驻留记忆T细胞。它们的不同生物学、功能和位置为皮肤中的免疫反应提供了充足的光谱。Foxp3+记忆调节性T细胞在维持皮肤稳态中起关键作用,其失调与不同的皮肤病理有关。皮肤也含有非经典T细胞群,如γδ T细胞、NK T细胞和mr1限制性T细胞。在过去的几年里,它们在皮肤稳态和对病原体的反应中的作用已经得到了很好的确立,然而,也有越来越多的证据表明它们在介导过敏性皮肤炎症和促进对过敏原的敏化方面的作用。在这篇综述中,我们提供了关于不同的T细胞亚群的最新概述,这些T细胞亚群在皮肤中的作用,并特别关注它们在过敏性皮肤炎症中的作用。
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引用次数: 1
The potential targets in immunotherapy of atherosclerosis. 动脉粥样硬化免疫治疗的潜在靶点。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 DOI: 10.1080/08830185.2021.1988591
Azin Aghamajidi, Melika Gorgani, Faezeh Shahba, Zahra Shafaghat, Nazanin Mojtabavi

Cardiovascular disease is the most common cause of death, which has the highest mortality rate worldwide. Although a diverse range of inflammatory diseases can affect the cardiovascular system, however, heart failure and stroke occur due to atherosclerosis. Atherosclerosis is a chronic autoinflammatory disease of small to large vessels in which different immune mediators are involved in lipid plaque formation and inflammatory vascular remodeling process. A better understanding of the pathophysiology of atherosclerosis may lead to uncovering immunomodulatory therapies. Despite present diagnostic and therapeutic methods, the lack of immunotherapy in the prevention and treatment of atherosclerosis is perceptible. In this review, we will discuss the promising immunological-based therapeutics and novel preventive approaches for atherosclerosis. This study could provide new insights into a better perception of targeted therapeutic pathways and biological therapies. [Formula: see text].

心血管疾病是最常见的死亡原因,是全世界死亡率最高的疾病。尽管多种炎症性疾病可影响心血管系统,但动脉粥样硬化导致心力衰竭和中风。动脉粥样硬化是一种小血管到大血管的慢性自身炎症性疾病,不同的免疫介质参与脂质斑块的形成和炎症性血管重构过程。更好地了解动脉粥样硬化的病理生理可能导致发现免疫调节疗法。尽管目前的诊断和治疗方法,免疫治疗在预防和治疗动脉粥样硬化方面的缺乏是显而易见的。在这篇综述中,我们将讨论基于免疫的治疗方法和新的预防动脉粥样硬化的方法。这项研究为更好地认识靶向治疗途径和生物治疗提供了新的见解。[公式:见正文]。
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引用次数: 1
Antibody engineering and its therapeutic applications. 抗体工程及其治疗应用。
IF 5 4区 医学 Q1 Medicine Pub Date : 2023-01-01 DOI: 10.1080/08830185.2021.1960986
Divya Kandari, Rakesh Bhatnagar

As a natural function, antibodies defend the host from infected cells and pathogens by recognizing their pathogenic determinants. Antibodies (Abs) gained wide acceptance with an enormous impact on human health and have predominantly captured the arena of bio-therapeutics and bio-diagnostics. The scope of Ab-based biologics is vast, and it is likely to solve many unmet clinical needs in future. The majority of attention is now devoted to developing innovative technologies for manufacturing and engineering Abs, better suited to satisfy human needs. The advent of Ab engineering technologies (AET) led to phenomenal developments leading to the generation of Abs-/Ab-derived molecules with desirable functional properties proportional to their expanding requirements. Evolution brought by AET, from the naturally occurring Ab forms to several advanced Ab formats and derivatives, was much needed as it is of great interest to the pharmaceutical industry. Thus, numerous advancements in AET have propelled success in therapeutic Ab development, along with the potential for ever-increasing improvements. Unique characteristics of Abs, such as its diversity, specificity, structural integrity and an array of possible applications, together inspire continuous innovation in the field. Overall, the AET could assist in conquer of several limitations of Abs in terms of their applicability in the field of therapeutics, diagnostics and research; AET has so far led to the production of next-generation Abs, which have revolutionized these arenas. Here in this review, we discuss the various distinguished engineering platforms for Ab development and the progress in modern therapeutics by the so-called "next-generation Abs."

作为一种自然功能,抗体通过识别其致病决定因素来保护宿主免受感染细胞和病原体的侵害。抗体(Abs)因其对人类健康的巨大影响而获得广泛接受,并已在生物治疗和生物诊断领域占据主导地位。基于抗体的生物制剂的应用范围是广阔的,未来很可能解决许多未满足的临床需求。现在,大多数注意力都集中在开发制造和工程Abs的创新技术上,以更好地满足人类的需求。抗体工程技术(AET)的出现导致了惊人的发展,导致产生具有理想功能特性的抗体/抗体衍生分子与其扩展需求成正比。AET带来的进化,从自然存在的Ab形式到几种高级Ab形式和衍生物,是非常需要的,因为它对制药工业非常感兴趣。因此,AET的许多进步推动了治疗性Ab开发的成功,以及不断增加的改进潜力。Abs的独特特性,如其多样性、特异性、结构完整性和一系列可能的应用,共同激发了该领域的不断创新。总的来说,AET可以帮助克服抗体在治疗、诊断和研究领域的适用性方面的几个局限性;到目前为止,AET已经导致了下一代抗体的生产,这已经彻底改变了这些领域。在这篇综述中,我们讨论了各种杰出的抗体开发工程平台以及所谓的“下一代抗体”在现代治疗学中的进展。
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引用次数: 5
期刊
International Reviews of Immunology
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