医学
免疫疗法
封锁
放射性配体
免疫检查点
联合疗法
癌症研究
放射性核素治疗
PD-L1
放射治疗
癌症
药理学
肿瘤科
核医学
内科学
受体
作者
Xuejun Wen,Xinying Zeng,Changrong Shi,Jia Liu,Yiren Zhang,Mengqi Shi,Jingchao Li,Haojun Chen,Rongqiang Zhuang,Xiaoyuan Chen,Xianzhong Zhang,Zhide Guo
标识
DOI:10.1002/adtp.202200193
摘要
Abstract The therapeutic alliance of 177 Lu radioligand therapy and immune checkpoint blockade (ICB) has gained increasing attention. This study aims to investigate the immunomodulatory effect (targeting‐triggering‐therapy) of 177 Lu‐DOTA‐EB‐cRGDfK ( 177 Lu‐DER) and to optimize the therapeutic efficacy by combining targeted radionuclide therapy (TRT) and ICB. Flow cytometry, immunofluorescence analysis, and RT‐qPCR are conducted to confirm the change of PD‐L1 expression. Tumor uptakes of 177 Lu‐DER in CT26 and MC38 colorectal tumor models are verified through single photon emission computed tomography imaging. Further, the radionuclide dose and the treatment schedule to optimize the therapeutic scheme are carefully titrated and the mechanism of the synergy between TRT and ICB is explored. The results demonstrate that PD‐L1 expression is upregulated after irradiation of 177 Lu. The combination of 9.25 MBq 177 Lu‐DER TRT with 200 µg αPD‐L1 immunotherapy significantly inhibits tumor growth and protects against tumor recurrence. It is also found that 4‐h interval is an effective time window between radioligand administration and ICB therapy. In conclusion, a promising scheme for tumor immunotherapy is realized based on the sequential administration of integrin α v β 3 ‐targeted radioligand and PD‐L1 immune checkpoint blocker, emphasizing the potential of combining radiotheranostics with ICB for precision cancer therapy.
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