PO.ET02.06 · 实验与分子治疗

比较由trastuzumab和人源化OKT3组成的潜在双特异性形式

Comparing potential bispecific formats comprising of trastuzumab and a humanized OKT3

海报缩略图:比较由trastuzumab和人源化OKT3组成的潜在双特异性形式
编号 4409 展板 17 时间 4/21 09:00–12:00 区域 Section 11 主讲 Sabrina Mateos Azpeitia
分会场 Antibody Technologies and Platforms 2
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作者与单位 Authors & Affiliations

Sabrina Mateos, Catherine Bladen, Abbie Hardisty, Emily Blackwood, Holly Guz, Stacey Walker, Stephen Anderson, Michael Fiebig

Vector Laboratories, Inc., Newark, CA

摘要 Abstract

中文摘要
目的:本摘要展示了Absolute Antibody(Vector Laboratories旗下公司)如何基于现有的单克隆抗体治疗性分子生成双特异性抗体,比较这些构建体及其可行性,以生产“表现良好的多特异性抗体”。 实验流程:我们的重组平台可将任何抗体转化为具有明确Fc突变的可定制多特异性形式,实现对效应功能的精确控制。以trastuzumab和一种人源化OKT3变体作为结合臂,我们生成并表达了一组双特异性构建体,将其纯化至高质量,并比较了它们的表达谱、单体含量和结合能力。这些变体现在作为参考集,用于正在进行的功能和生物物理表征研究。 结论:近期报告列出了79种处于临床阶段的多特异性抗体,而Absolute Antibody(Vector Laboratories旗下公司)已生产了180多种工程化形式。在本研究中,我们构建并分析了17种双特异性设计,揭示含Fc的架构、scFv位置和界面工程强烈影响表达和稳定性。该参考组突出了设计选择如何塑造双特异性性能,并可用于合作研究。
查看英文原文 English abstract
Purpose: This abstract showcases how Absolute Antibody (a Vector Laboratories company) generate bi-specific antibodies based on existing monoclonal antibody therapeutics molecules, compare the constructs and feasibility in order to produce “well-behaved multi-specifics”. Experimental Procedures: Our recombinant platform converts any antibody into customizable multispecific formats with defined Fc mutations, enabling precise control of effector function. Using trastuzumab and a humanized OKT3 variant as binding arms, we generated and expressed a panel of bispecific constructs, purified them to high quality, and compared their expression profiles, monomer content, and binding. These variants now serve as a reference set for ongoing functional and biophysical characterization studies. Conclusions: Recent reports list 79 multi-specific antibodies in the clinic, while Absolute Antibody (a Vector Laboratories company) has produced more than 180 engineered formats. In this study, we built and analyzed 17 bispecific designs, revealing that Fc-containing architectures, scFv placement, and interface engineering strongly affect expression and stability. This reference panel highlights how design choices shape bispecific performance and is available for collaborative research.
利益披露 Disclosure
S. Mateos, None.. C. Bladen, None.. A. Hardisty, None.. E. Blackwood, None.. H. Guz, None.. S. Walker, None.. S. Anderson, None.. M. Fiebig, None.

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