PO.ET08.01 · 实验与分子治疗

用于评估靶向放射性配体疗法的、代表多种肿瘤适应症的细胞系来源异种移植模型组的开发与验证

Development and validation of a panel of cell line derived xenograft models representing multiple tumor indications for the evaluation of targeted radioligand therapeutics

编号 4647 展板 24 时间 4/21 09:00–12:00 区域 Section 19 主讲 Michael Batey, M Phil
分会场 Strategies to Enhance the Therapeutic Index of Radiotherapy
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作者与单位 Authors & Affiliations

Michael Batey, James Suchy, Taylor Hotz, Michael Bruce, Jennifer Tavares, Erin Snay, Neil Rollins, Jackson Chan, Karen Gelinas, Kayla Duval, William Maccuaig, Michael Milhollen, Michelle Petrozzi, Kyeara Mack-Henry, Soumya Ullas

Perceptive Discovery, Boston, MA

摘要 Abstract

中文摘要
靶向放射性配体疗法(RLT)代表了精准肿瘤学的一项重大进展,能够在选择性靶向肿瘤的同时最大限度地减少对健康组织的损伤。然而,创新性RLT药物的开发常常受制于评估靶点特异性疗效所需的稳健、经充分验证的临床前模型的匮乏。在此,我们展示了一个全面的体外筛选检测和体内细胞系来源异种移植模型组的开发与验证,其中包括Colo205、MiaPaca2、SHP-77、HT29、A549、LNCaP和22Rv1等模型,这些模型表达与放射性配体疗法相关的关键靶点。这些模型为在这一快速发展的领域中评估新型药物提供了理想途径,涵盖TROP2、CAIX、DLL3、FAP和PSMA等靶点,横跨包括胶质母细胞瘤、结直肠癌、肺癌、胰腺癌和前列腺癌在内的一系列适应症。我们还讨论了体内和离体成像技术的应用,例如单光子发射计算机断层扫描(SPECT)和低温荧光断层扫描(CFT)。这些研究凸显了这些平台在广泛靶向疗法的临床前开发中的实用价值,其潜在应用横跨包括RLT、抗体-药物偶联物(ADC)和小分子在内的多种治疗模式。
查看英文原文 English abstract
Targeted radioligand therapy (RLT) represents a significant advancement in precision oncology, enabling selective tumor targeting while minimizing damage to healthy tissue. However, the development of innovative RLT agents is often hindered by the limited availability of robust, well-validated preclinical models needed to evaluate target-specific efficacy. Here, we demonstrate the development and validation of a comprehensive panel of in vitro screening assays and in vivo cell line-derived xenografts, including models such as Colo205, MiaPaca2, SHP-77, HT29, A549, LNCaP, and 22Rv1, which express key targets relevant to radioligand therapy. These models provide an ideal pathway for evaluating novel agents in this rapidly growing field, covering targets such as TROP2, CAIX, DLL3, FAP, and PSMA across a range of indications including glioblastoma, colorectal, lung, pancreatic, and prostate cancers. We also discuss the use of in vivo and ex vivo imaging techniques such as single photon emission computed tomography (SPECT) and cryo fluorescence tomography (CFT) . These studies highlight the utility of these platforms for the preclinical development of a wide range of target-based therapies, with potential applications spanning multiple therapeutic modalities including RLT, antibody-drug conjugates (ADCs), and small molecules.
利益披露 Disclosure
M. Batey, None.. J. Suchy, None.. T. Hotz, None.. M. Bruce, None.. J. Tavares, None.. E. Snay, None.. N. Rollins, None.. J. Chan, None.. K. Gelinas, None.. K. Duval, None.. W. Maccuaig, None.. M. Milhollen, None.. M. Petrozzi, None.. K. Mack-Henry, None.. S. Ullas, None.

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