不同形式的t细胞参与双特异性抗体的可制造性和功能评估。

IF 5.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
mAbs Pub Date : 2023-01-01 DOI:10.1080/19420862.2023.2231129
Han Ping Loh, Farouq Bin Mahfut, Serene W Chen, Yuhan Huang, Jianxin Huo, Wei Zhang, Kong Peng Lam, Shengli Xu, Yuansheng Yang
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引用次数: 0

摘要

t细胞参与双特异性抗体(T-bsAbs)是一种很有前途的癌症治疗免疫疗法,因为它们能够将t细胞重定向到破坏肿瘤细胞。已经开发了许多T-bsAb格式,每种格式在可发展性,免疫原性,效应功能和药代动力学方面都有优点和缺点。在这里,我们系统地比较了使用八种不同格式生产的t - bsab,评估了t - bsab的分子设计对其可制造性和功能的影响。这八种T-bsAb格式是使用抗原结合片段(fab)和与免疫球蛋白g的可结晶片段(Fc)结构域连接的抗体的单链可变片段(scFvs)构建的。为了确保生长和生产数据的公平比较,我们使用重组酶介导的盒式交换技术来生成产生T-bsAb的CHO细胞系。对制备的t - bsab进行了纯化、回收、结合能力和生物活性的评价。我们的研究结果表明,scFv构建块数量的增加会对bsab的可制造性产生不利影响,而功能则受到多种因素的综合影响,包括靶向部分的结合亲和力和亲切性,以及格式的灵活性和几何形状。这些结果为研究格式设计对t - bsab的最佳生产和功能的影响提供了有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies.

Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies.

Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies.

Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies.

T-cell-engaging bispecific antibodies (T-bsAbs) are promising immunotherapies for cancer treatment due to their capability of redirecting T-cells toward destroying tumor cells. Numerous T-bsAb formats have been developed, each with advantages and disadvantages in terms of developability, immunogenicity, effector functions, and pharmacokinetics. Here, we systematically compared T-bsAbs produced using eight different formats, evaluating the effect of molecular design of T-bsAbs on their manufacturability and functionality. These eight T-bsAb formats were constructed using antigen-binding fragments (Fabs) and single-chain variable fragments (scFvs) of antibodies linked to the crystallizable fragment (Fc) domain of immunoglobulin G. To ensure a fair comparison of growth and production data, we used recombinase-mediated cassette exchange technology to generate the T-bsAb-producing CHO cell lines. The produced T-bsAbs were assessed for their purification profile and recovery, binding capability, and biological activities. Our findings indicated that the manufacturability of bsAbs was adversely affected with increased number of scFv building blocks, while the functionality was affected by the combination of multiple factors, including the binding affinity and avidity of targeting moieties and the flexibility and geometry of formats. These results provide valuable insights into the impact of the format design on the optimal production and function of T-bsAbs.

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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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