Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery.

IF 5.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL mAbs Pub Date : 2024-01-01 Epub Date: 2024-11-28 DOI:10.1080/19420862.2024.2435476
Christine N Vuong, Kevin M Reynolds, Gerry S Rivera, Baisen Zeng, Zahra Karimpourkalou, Manith Norng, Yulei Zhang, Robayet Chowdhury, Darlene Pedersen, Melissa Pantoja, Ellen Collarini, Swetha Garimalla, Shelley Izquierdo, Eric G Vajda, Brett Antonio, Devendra B Srivastava, Marie-Cecile van de Lavoir, Yasmina Abdiche, William Harriman, Philip A Leighton
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引用次数: 0

Abstract

Heavy chain-only antibodies have found many applications where conventional heavy-light heterodimeric antibodies are not favorable. Heavy chain-only antibodies with their single antigen-binding domain offer the advantage of a smaller size and higher stability relative to conventional antibodies, and thus, the potential for novel targeting modalities. Domain antibodies have commonly been sourced from camelids with ex-vivo humanization or transgenic rodents expressing heavy chains without light chains, but these host species are all mammalian, limiting their capacity to elicit robust immune responses to conserved mammalian targets. We have developed transgenic chickens expressing heavy chain-only antibodies with a human variable region to combine the superior target recognition advantages of a divergent, non-mammalian host with the ability to discover single-domain binders. These birds produce robust immune responses, consisting of antigen-specific antibodies targeting diverse epitopes with a range of affinities. Biophysical attributes are favorable, with good developability profiles and low predicted immunogenicity.

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在转基因鸡体内使用稳定的人类 VH 的纯重链抗体,以发现治疗性抗体。
纯重链抗体在传统的重链-轻链异源二聚体抗体不适用的领域有很多应用。与传统抗体相比,具有单一抗原结合结构域的纯重链抗体具有体积更小、稳定性更强的优势,因此有可能成为新的靶向模式。领域抗体通常来自体内外人源化的驼科动物或表达重链而不表达轻链的转基因啮齿类动物,但这些宿主物种都是哺乳动物,限制了它们对哺乳动物保守靶点引起强大免疫反应的能力。我们开发了表达带有人类可变区的纯重链抗体的转基因鸡,将不同的非哺乳动物宿主的目标识别优势与发现单域结合体的能力结合起来。这些鸟类产生了强大的免疫反应,包括针对不同表位的抗原特异性抗体,具有各种亲和力。生物物理属性良好,具有良好的可开发性和较低的预测免疫原性。
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来源期刊
mAbs
mAbs 工程技术-仪器仪表
CiteScore
10.70
自引率
11.30%
发文量
77
审稿时长
6-12 weeks
期刊介绍: mAbs is a multi-disciplinary journal dedicated to the art and science of antibody research and development. The journal has a strong scientific and medical focus, but also strives to serve a broader readership. The articles are thus of interest to scientists, clinical researchers, and physicians, as well as the wider mAb community, including our readers involved in technology transfer, legal issues, investment, strategic planning and the regulation of therapeutics.
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