In situ editing of tumour cell membranes induces aggregation and capture of PD-L1 membrane proteins for enhanced cancer immunotherapy

Nat Commun. 2024 Nov 9;15(1):9723. doi: 10.1038/s41467-024-54081-9.

Abstract

Immune checkpoint blockade (ICB) therapy has emerged as a new therapeutic paradigm for a variety of advanced cancers, but wide clinical application is hindered by low response rate. Here we use a peptide-based, biomimetic, self-assembly strategy to generate a nanoparticle, TPM1, for binding PD-L1 on tumour cell surface. Upon binding with PD-L1, TPM1 transforms into fibrillar networks in situ to facilitate the aggregation of both bound and unbound PD-L1, thereby resulting in the blockade of the PD-1/PD-L1 pathway. Characterizations of TPM1 manifest a prolonged retention in tumour ( > 7 days) and anti-cancer effects associated with reinvigorating CD8+ T cells in multiple mice tumour models. Our results thus hint TPM1 as a potential strategy for enhancing the ICB efficacy.

MeSH terms

  • Animals
  • B7-H1 Antigen* / immunology
  • B7-H1 Antigen* / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • Cell Line, Tumor
  • Cell Membrane* / metabolism
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy* / methods
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Peptides / metabolism
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors
  • CD274 protein, human
  • Membrane Proteins
  • Peptides
  • Programmed Cell Death 1 Receptor