Wang, Sheng, Xu, Duo, Wang, Yuan, Zhou, Yuehua, Xiao, Lingyan, Li, Fang, Tu, Jingyao, Qin, Wan, Tian, Sidan, Zheng, Bolong, Wang, Yihua, Yuan, Xianglin, Liu, Yuanhui and Liu, Bo (2025) A bifunctional antibody targeting PD-1 and TGF-β signaling has antitumor activity in combination with radiotherapy and attenuates radiation-induced lung injury. Cancer Immunology Research, 2025. (1158/2326-6066.CIR-23-0903).
Abstract
Radio-immunotherapy has antitumor activity but also causes toxicity, which limits its clinical application. JS-201 is a dual antibody targeting PD-1 and TGF-β signaling. We investigated the antitumour effect of JS-201 combined with radiotherapy and the effect on radiation-induced lung injury (RILI). Different tumor models were established to detect the antitumor effects of the combination of JS-201 and RT, and RILI models were established to observe the effects of JS-201. Transcriptome sequencing showed that JS-201 optimized the TME by inhibiting extracellular matrix formation and angiogenesis. Combining JS-201 with radiotherapy further increased the inflammatory response and immune infiltration and showed great abscopal effects in LLC-luc models. Single-cell sequencing demonstrated that JS-201 reduced fibroblast proliferation by inhibiting the TGF-β/Smad pathway and the release of neutrophil extracellular traps mediated by ROS, thereby relieving radiation-induced pulmonary fibrosis. In conclusion, the JS-201 and radiotherapy combination enhances antitumor effects while mitigating acute and chronic RILI, and it may have potential for translational investigation as a cancer treatment strategy.
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