A Novel d-Peptide Identified by Mirror-Image Phage Display Blocks TIGIT/PVR for Cancer Immunotherapy
Xiuman Zhou
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
These authors contributed equally to this work.
Search for more papers by this authorChao Zuo
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 China
These authors contributed equally to this work.
Search for more papers by this authorWanqiong Li
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorWeiwei Shi
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 China
Search for more papers by this authorXiaowen Zhou
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorHongfei Wang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorShaomeng Chen
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorJiangfeng Du
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorGuanyu Chen
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorWenjie Zhai
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorWenshan Zhao
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYahong Wu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorProf. Yuanming Qi
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorCorresponding Author
Prof. Lei Liu
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 China
Search for more papers by this authorCorresponding Author
Prof. Yanfeng Gao
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorXiuman Zhou
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
These authors contributed equally to this work.
Search for more papers by this authorChao Zuo
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 China
These authors contributed equally to this work.
Search for more papers by this authorWanqiong Li
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorWeiwei Shi
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 China
Search for more papers by this authorXiaowen Zhou
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorHongfei Wang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorShaomeng Chen
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorJiangfeng Du
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorGuanyu Chen
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorWenjie Zhai
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorWenshan Zhao
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYahong Wu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorProf. Yuanming Qi
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorCorresponding Author
Prof. Lei Liu
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 China
Search for more papers by this authorCorresponding Author
Prof. Yanfeng Gao
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
Search for more papers by this authorAbstract
The low response rate and adaptive resistance of PD-1/PD-L1 blockade demands the studies on novel therapeutic targets for cancer immunotherapy. We discovered that a novel immune checkpoint TIGIT expressed higher than PD-1 in many tumors especially anti-PD-1 resistant tumors. Here, mirror-image phage display bio-panning was performed using the d-enantiomer of TIGIT synthesized by hydrazide-based native chemical ligation. d-peptide DTBP-3 was identified, which could occupy the binding interface and effectively block the interaction of TIGIT with its ligand PVR. DTBP-3 showed proteolytic resistance, tumor tissue penetrating ability, and significant tumor suppressing effects in a CD8+ T cell dependent manner. More importantly, DTBP-3 could inhibit tumor growth and metastasis in anti-PD-1 resistant tumor model. This is the first d-peptide targeting TIGIT, which could serve as a potential candidate for cancer immunotherapy.
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