PO.ET02.01 · 实验与分子治疗
RenLite®转基因小鼠为加速全球全人源双特异性抗体或ADC的开发提供高质量平台
RenLite ® transgenic mice provide a high-quality platform for accelerating the development of fully human bispecific antibodies or ADCs worldwide
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摘要 Abstract
中文摘要
双特异性抗体(BsAb)和双特异性抗体偶联药物(BsADC)的全球开发正经历爆发式增长。然而,关键痛点依然存在——重轻链错配、靶点协同不足、毒性控制不佳以及生产工艺复杂。虽然已开发出新技术来解决这些问题,但药物开发在靶点组合选择、漫长的抗体发现周期以及低临床转化成功率方面仍面临障碍。百奥赛图RenLite®小鼠可生成具有共同轻链的全人源抗体候选物,从而能够后续组装错配最小化且可开发性优异的BsAb——为下游CMC开发赋予优势。此外,共同轻链有助于筛选不同的BsAb形式、载荷偶联和功能评价——支持多样化BsAb或BsAb-ADC模式的发现。迄今为止,凭借RenLite®及其新型BsADC平台,百奥赛图已生成多个临床前BsAb-ADC候选物。例如,DM001(抗TROP2×EGFR)具有良好的可开发性,在七种不同的患者来源异种移植(PDX)模型中展现出强效的肿瘤抑制活性;DM005(抗EGFR×MET)纯度高、偶联性能良好,在肺癌PDX模型中表现出卓越的特异性和抗肿瘤疗效。这些BsADC候选物具有巨大的临床开发潜力。凭借其RenLite®平台和初步筛选,百奥赛图已建立了一个涵盖200多种肿瘤相关抗原(TAA)的抗体库。这使研究人员能够利用体外/体内疗效平台轻松开展快速筛选、灵活配对和靶点协同验证,加速BsAb/BsADC的开发,并提升抗癌疗法的临床转化成功率。
查看英文原文 English abstract
Global development of bispecific antibodies (BsAbs) and bispecific antibody-drug conjugates (BsADCs) is undergoing explosive growth. However, key pain points persist-heavy-light chain mismatch, inadequate target synergy, poor toxicity control, and complex manufacturing. While novel technologies have been developed to address these issues, drug development still faces hurdles in target combination selection, lengthy antibody discovery cycles, and low clinical translation success rates.Biocytogen RenLite ® mice generate fully human antibody candidates with a common light chain, enabling subsequent assembly of BsAbs with minimized chain mismatch and excellent developability-conferring advantages for downstream CMC development. Additionally, the common light chain facilitates screening of different BsAb formats, payload conjugation, and function evaluation-supporting the discovery of diverse BsAb or BsAb-ADC modalities.To date, leveraging RenLite ® and its novel BsADC platform, Biocytogen has generated multiple preclinical BsAb-ADC candidates. For example, DM001 (anti-TROP2×EGFR), with good developability, demonstrates potent tumor-suppressive activity in seven various patient-derived xenograft (PDX) models; DM005 (anti-EGFR×MET), with high purity and good conjugation property, exhibits outstanding specificity and anti-tumor efficacy in lung cancer PDX models. These BsADC candidates hold great clinical development potential.Leveraging its RenLite ® platform and preliminary screening, Biocytogen has built an antibody library covering over 200 tumor-associated antigens (TAAs). This lets researchers easily conduct rapid screening, flexible pairing, and target synergy validation using in vitro / in vivo efficacy platforms, speeding up BsAb/ BsADC development and boosting clinical translation success of anticancer therapies.
利益披露 Disclosure
J. Hsu, None..
W. Zhang, None..
J. Du, None..
Z. Li, None..
Y. Zhang, None..
Y. Han, None..
C. Shang, None..
Y. Yang, None.