A Novel d‐Peptide Identified by Mirror‐Image Phage Display Blocks TIGIT/PVR for Cancer Immunotherapy. Issue 35 (8th June 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 35(2020)
• Page Start: 15114
• Page End: 15118
• Publication Date: 2020-06-08
• Subjects: cancer immunotherapy -- immune checkpoint -- mirror-image phage display -- peptide -- TIGIT; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202002783
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : The d ‐peptide D TBP‐3 was identified, which could effectively block TIGIT/PVR interaction. D TBP‐3 could inhibit tumor growth and metastasis in anti‐PD‐1 resistant tumor model and could serve as a potential candidate for cancer immunotherapy.