B7-H4靶向放射治疗可实现实体瘤模型的精确成像和有效治疗
B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models.
摘要(中文译文)
B7-H4是一种新兴的免疫调节检查点，在实体瘤中广泛过表达，在正常组织中存在最少，使其成为靶向成像和治疗的有吸引力的候选者。在这里，我们开发和评估了一种B7-H4导向的放射治疗抗体，该抗体分别用[89Zr]标记用于PET成像，用[177Lu]或[225Ac]标记用于β或α粒子治疗。[89Zr]-免疫PET使B7-H4表达的定量全身可视化成为可能，并可靠地区分高、中、阴性表达的肿瘤。用[177Lu]-或[225Ac]-偶联抗体进行放射治疗显示出强大的抗原依赖性抗肿瘤活性，包括单次给药后B7-H4-高表达异种移植物的完全和持久消退，同时对B7-H4-阴性肿瘤的影响很小。两种治疗结构均耐受良好，仅引起短暂、可逆的骨髓抑制，没有持续的肝、肾或组织病理学毒性。这些发现将B7-H4确定为综合成像和放射性核素治疗的有前景的靶点，并为B7-H4定向放射治疗策略的未来发展提供了临床前基础。
Abstract
B7-H4 is an emerging immunoregulatory checkpoint broadly overexpressed across solid tumors and minimally present in normal tissues, making it an attractive candidate for targeted imaging and therapy. Here, we develop and evaluate a B7-H4-directed radiotheranostic antibody labeled with [Zr] for PET imaging and with either [Lu] or [Ac] for β- or α-particle therapy, respectively. [Zr]-immunoPET enabled quantitative, whole-body visualization of B7-H4 expression and reliably distinguished high, intermediate, and negative-expressing tumors. Radiotherapy with [Lu]- or [Ac]-conjugated antibody exhibited potent, antigen-dependent antitumor activity, including complete and durable regressions in B7-H4-high expressing xenografts after a single administration, while having a minimal effect on B7-H4-negative tumors. Both therapeutic constructs were well tolerated, causing only transient, reversible myelosuppression without sustained hepatic, renal, or histopathologic toxicity. These findings identify B7-H4 as a promising target for integrated imaging and radionuclide therapy and provide a preclinical foundation for the future development of B7-H4-directed radiotheranostic strategies.
如何引用
AMA
Behnaz Ghaemi, Colleen P Olkowski, Falguni Basuli, Jianfeng Shi, Peter L Choyke, Orit Jacobson. B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models.. Science advances. 2026; doi:10.1126/sciadv.aef8428.
APA
Behnaz Ghaemi, Colleen P Olkowski, Falguni Basuli, Jianfeng Shi, Peter L Choyke, Orit Jacobson (2026). B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models.. Science advances. https://doi.org/10.1126/sciadv.aef8428
GB/T 7714
Behnaz Ghaemi, Colleen P Olkowski, Falguni Basuli, Jianfeng Shi, Peter L Choyke, Orit Jacobson. B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models.[J]. Science advances, 2026 doi:10.1126/sciadv.aef8428.
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