2. Academic Validation
  3. Glycoengineering-based anti-PD-1-iRGD peptide conjugate boosts antitumor efficacy through T cell engagement

Glycoengineering-based anti-PD-1-iRGD peptide conjugate boosts antitumor efficacy through T cell engagement

  • Cell Rep Med. 2024 Jun 18;5(6):101590. doi: 10.1016/j.xcrm.2024.101590.
Yunfeng Pan 1,  Qi Xue 2,  Yi Yang 3,  Tao Shi 4,  Hanbing Wang 4,  Xueru Song 4,  Yuting Luo 4,  Wenqi Liu 4,  Shiji Ren 4,  Yiran Cai 4,  Yang Nie 4,  Zhentao Song 3,  Baorui Liu 4,  Jie P Li 5,  Jia Wei 6
Affiliations

Affiliations

  • 1 Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
  • 2 Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
  • 3 Glyco-therapy Biotechnology Co. Ltd., Building 12, Hangzhou Pharmaceutical Town, 291 Fucheng Road, Xiasha Street, Qiantang District, Hangzhou, China.
  • 4 Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 5 Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China. Electronic address: jieli@nju.edu.cn.
  • 6 Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China; Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China. Electronic address: jiawei99@nju.edu.cn.
PMID: 38843844 DOI: 10.1016/j.xcrm.2024.101590
Abstract

Despite the important breakthroughs of Immune Checkpoint inhibitors in recent years, the objective response rates remain limited. Here, we synthesize programmed cell death protein-1 (PD-1) antibody-iRGD cyclic peptide conjugate (αPD-1-(iRGD)2) through glycoengineering methods. In addition to enhancing tissue penetration, αPD-1-(iRGD)2 simultaneously engages tumor cells and PD-1+ T cells via dual targeting, thus mediating tumor-specific T cell activation and proliferation with mild effects on non-specific T cells. In multiple syngeneic mouse models, αPD-1-(iRGD)2 effectively reduces tumor growth with satisfactory biosafety. Moreover, results of flow cytometry and single-cell RNA-seq reveal that αPD-1-(iRGD)2 remodels the tumor microenvironment and expands a population of "better effector" CD8+ tumor infiltrating T cells expressing stem- and memory-associated genes, including Tcf7, Il7r, Lef1, and Bach2. Conclusively, αPD-1-(iRGD)2 is a promising antibody conjugate therapeutic beyond antibody-drug conjugate for Cancer Immunotherapy.

Keywords

BiTEs; PD-1 antibody; glycoengineering; iRGD; immunotherapy; peptide antibody conjugate.

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