ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicResearch on Nanomaterials in Tumor Diagnosis and Therapy, Volume IIView all 8 articles
Dual Checkpoint Blockade of PD-1 and TIM-3 by Engineered Hybrid Nanovesicles for Enhanced Cancer Immunotherapy
Provisionally accepted
- 1The First People's Hospital of Wenling, Wenling, China
- 2Beihua University, Jilin, China
- 3Taizhou University, Taizhou, China
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T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is an inhibitory receptor expressed on immune cells, and its co-expression with programmed cell death protein 1 (PD-1) is an established mechanism of immune exhaustion and resistance to checkpoint blockade. To overcome this, we developed PD-1/TIM-3-decorated nanovesicles (PD-1/TIM-3 NVs) for combination immunotherapy against colorectal cancer. These vesicles selectively engaged the ligands PD-L1 and Galectin-9. In mice bearing CT26 xenografts, PD-1/TIM-3 NVs suppressed tumor growth by 69.0%, remodeled the tumor microenvironment by enhancing CD8+ T cell infiltration and activation, and depleting immunosuppressive regulatory T cells. Our findings highlight the promising potential of simultaneous PD-1 and Tim-3 blockade for treating advanced tumors.
Keywords: PD-1, TIM-3, cell membrane nanovesicle, antitumor immunity, Dual checkpoint blockade
Received: 15 Sep 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Xue, Guan, Huang, Fan, Guo, Liang, Guan and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xingang Guan
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