Cancer Immunology, Immunotherapy (May 2025)

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

  • Yirong Wu,
  • Lanqun Qin,
  • Jiayu Wang,
  • Ziyao Xie,
  • Xinyu Su,
  • Xiang Li,
  • Yueling Yang,
  • Rong Huang,
  • Mengke Zhao,
  • Lianjun Zhao,
  • Zhengyun Zou

DOI
https://doi.org/10.1007/s00262-025-04077-1
Journal volume & issue
Vol. 74, no. 7
pp. 1 – 16

Abstract

Read online

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