Premium
A Novel d ‐Peptide Identified by Mirror‐Image Phage Display Blocks TIGIT/PVR for Cancer Immunotherapy
Author(s) -
Zhou Xiuman,
Zuo Chao,
Li Wanqiong,
Shi Weiwei,
Zhou Xiaowen,
Wang Hongfei,
Chen Shaomeng,
Du Jiangfeng,
Chen Guanyu,
Zhai Wenjie,
Zhao Wenshan,
Wu Yahong,
Qi Yuanming,
Liu Lei,
Gao Yanfeng
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202002783
Subject(s) - tigit , cancer research , immunotherapy , cancer immunotherapy , phage display , t cell , panning (audio) , peptide , immune system , chemistry , biology , immunology , biochemistry , paleontology , zoom , lens (geology)
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 D TBP‐3 was identified, which could occupy the binding interface and effectively block the interaction of TIGIT with its ligand PVR. D TBP‐3 showed proteolytic resistance, tumor tissue penetrating ability, and significant tumor suppressing effects in a CD8 + T cell dependent manner. More importantly, D TBP‐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.