PO.IM01.13 · 免疫学
利用AI增强的多组学发现用于ADC开发的新型肿瘤选择性靶点
Leveraging AI-enhanced multi-omics discovery of novel tumor-selective targets for ADC development
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
TenSixty Biosciences采用创新的AI增强多组学发现框架，以推动新一代抗体药物偶联物（ADC）的开发。这一整合方法通过结合以下方面，鉴定出具有高治疗潜力的新型肿瘤选择性靶点：
1. 与先进AI分析整合的多维组学分析，以发掘具有治疗相关性的癌症靶点
2. 专门的蛋白质组学分析，聚焦于揭示靶点肿瘤特异性变体的独特翻译后修饰（PTM），从而实现增强的肿瘤选择性靶向
3. 专有的抗体发现与工程改造，针对这些变体生成肿瘤选择性抗体，产出高效的ADC候选物
将该框架应用于小细胞肺癌（SCLC），鉴定出一个表现出肿瘤特异性低糖基化的新型治疗靶点。针对由糖基化改变所暴露表位的抗体表现出卓越的肿瘤选择性和显著增强的ADC疗效。跨发现和开发阶段的AI驱动整合进一步加速了靶点验证和候选物优化。
查看英文原文 English abstract
TenSixty Biosciences employs an innovative AI-enhanced multi-omics discovery framework to enable the development of next-generation antibody-drug conjugates (ADCs). This integrated approach identified novel tumor-selective targets with high therapeutic potential by combining:
1. Multi-dimensional omics analysis integrated with advanced AI analytics to uncover therapeutically relevant cancer targets
2. Specialized proteomic profiling focused on unique post-translational modifications (PTMs) that reveal tumor-specific variants of targets, enabling enhanced tumor-selective targeting
3. Proprietary antibody discovery and engineering generates tumor-selective antibodies directed against these variants, yielding highly potent ADC candidates
Applied to small cell lung cancer (SCLC), this framework identified a novel therapeutic target exhibiting tumor-specific hypoglycosylation. Antibodies directed against the epitope exposed by altered glycosylation showed exceptional tumor selectivity and markedly enhanced ADC efficacy. AI-driven integration across discovery and development stages further accelerated target validation and candidate optimization.
利益披露 Disclosure
D. Montoro,
TenSixty Biosciences Employment, g., Board of Directors, non-salaried role), Stock.
C. Muus,
TenSixty Biosciences Employment, g., Board of Directors, non-salaried role), Stock.
K. Jagadeesh,
TenSixty Biosciences Employment, g., Board of Directors, non-salaried role), Stock.
C. Rouleau,
TenSixty Biosciences Employment, Stock.
Y. Shi,
TenSixty Biosciences Employment, Stock.
S. Takahashi,
TenSixty Biosciences Employment, Stock.
J. Meador,
TenSixty Biosciences Employment, Stock.
R. Singh,
TenSixty Biosciences Employment, Stock.