PO.ET08.01 · 实验与分子治疗
验证一组表达成纤维细胞活化蛋白的细胞系来源异种移植模型作为靶向放射性配体治疗药物开发平台
Validation of a panel of fibroblast activation protein expressing cell line derived xenograft models as a platform for the development of targeted radioligand therapeutics
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作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
靶向放射性配体治疗（RLT）已成为精准肿瘤学的一种有前景的策略，能够选择性靶向肿瘤，同时减少对健康组织的附带损伤。然而，推进新型RLT药物的一个主要挑战是缺乏经过充分验证的临床前模型来评估靶点特异性疗效。成纤维细胞活化蛋白（FAP）是一种膜结合蛋白，在正常组织中表达极少，但在癌症相关成纤维细胞和胶质母细胞瘤（GBM）细胞中高度普遍存在，代表了一个有吸引力的治疗靶点。FAP-2286是一种以镥-177（177Lu）放射性标记的FAP结合肽，具有作为成像和治疗药物的双重潜力。在本研究中，我们评估了靶点表达，并比较了177Lu-FAP-2286在多种携带皮下细胞系来源肿瘤的免疫缺陷小鼠模型中的抗肿瘤疗效。我们的发现强调了模型选择在临床前开发中的关键作用，并凸显了其对RLT项目合理决策的重要性。
查看英文原文 English abstract
Targeted radioligand therapy (RLT) has emerged as a promising strategy for precision oncology, enabling selective tumor targeting while reducing collateral damage to healthy tissue. A major challenge in advancing novel RLT agents, however, is the limited availability of well-validated preclinical models for assessing target-specific efficacy. Fibroblast Activation Protein (FAP), a membrane-bound protein with minimal expression in normal tissues but high prevalence in cancer-associated fibroblasts and glioblastoma (GBM) cells, represents an attractive therapeutic target. FAP-2286, a FAP-binding peptide radiolabeled with lutetium-177 ( 177 Lu), offers potential as both an imaging and therapeutic agent. In this study, we evaluate target expression and compare the anti-tumor efficacy of 177 Lu-FAP-2286 across multiple immunocompromised mouse models bearing subcutaneous, cell line-derived tumors. Our findings underscore the critical role of model selection in preclinical development and highlight its importance for rational decision-making in RLT programs.
利益披露 Disclosure
M. Batey, None..
J. Suchy, None..
T. Hotz, None..
M. Milhollen, None..
K. Duval, None..
J. Chan, None..
K. Gelinas, None..
M. Bruce, None..
M. Petrozzi, None..
W. Maccuaig, None..
N. Rollins, None..
J. Tavares, None..
E. Snay, None..
K. Mack-Henry, None..
S. Ullas, None.