2. Academic Validation
  3. Stabilized iRGD modification enhances NY-ESO-1 TCR-T infiltration in solid tumors and synergizes with PD-1 blockade

Stabilized iRGD modification enhances NY-ESO-1 TCR-T infiltration in solid tumors and synergizes with PD-1 blockade

  • Cancer Immunol Immunother. 2025 May 30;74(7):226. doi: 10.1007/s00262-025-04077-1.
Yirong Wu 1,  Lanqun Qin 2,  Jiayu Wang 3,  Ziyao Xie 1,  Xinyu Su 1,  Xiang Li 1,  Yueling Yang 3,  Rong Huang 1,  Mengke Zhao 2,  Lianjun Zhao 1,  Zhengyun Zou 4 5 6
Affiliations

Affiliations

  • 1 Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
  • 2 Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
  • 3 Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
  • 4 Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China. zouzhengyun@njglyy.com.
  • 5 Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. zouzhengyun@njglyy.com.
  • 6 Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China. zouzhengyun@njglyy.com.
PMID: 40445421 DOI: 10.1007/s00262-025-04077-1
Abstract

Currently, two main challenges in Cancer Immunotherapy commonly hinder the application of T cell receptor-modified T cell (TCR-T) therapy in the treatment of solid tumors, including the limited ability of T cells to infiltrate solid tumor tissues and the immunosuppressive signals that restrain the anti-tumor efficacy of T cells. In this study, we constructed NY-ESO-1-specific TCR-T and introduced polyethylene glycol-phospholipids (PEG-lipids) to stably modify NY-ESO-1 TCR-T with nonapeptide iRGD, aiming to enhance the penetrability of T cells in vivo, then we combined iRGD-modified NY-ESO-1 TCR-T (iRGD-NY-ESO-1 TCR-T) with PD-1 blockade to alleviate immunosuppressive signals. In result, it is suggested that stably modifying NY-ESO-1 TCR-T with iRGD is a simple and effective strategy to enable TCR-T to target and penetrate solid tumor tissues. Besides, the combination of iRGD-NY-ESO-1 TCR-T with PD-1 blockade presents a novel synergistic strategy for the treatment of refractory NY-ESO-1-positive solid tumors.

Keywords

NY-ESO-1; PD-1 blockade; Solid tumors; TCR-T therapy; iRGD.

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