Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors

Nanoscale. 2021 Sep 17;13(35):15010-15020. doi: 10.1039/d1nr04001d.

Abstract

For effective targeted therapy of cancer with chemotherapy-loaded nanoparticles (NPs), antigens that are selective for cancer cells should be targeted to minimise off-tumour toxicity. Human leukocyte antigens (HLAs) are attractive cancer targets as they can present peptides from tumour-selective proteins on the cell surface, which can be recognised by T cells via T cell receptors (TCRs). In this study, docetaxel-loaded polymeric NPs were conjugated to recombinant affinity-enhanced TCRs to target breast cancer cells presenting a tumour-selective peptide-HLA complex. The TCR-conjugated nanoparticles enabled enhanced delivery of docetaxel and induced cell death through tumour-specific peptide-HLA targeting. These in vitro data demonstrate the potential of targeting tumour-restricted peptide-HLA epitopes using high affinity TCR-conjugated nanoparticles, representing a novel treatment strategy to deliver therapeutic drugs specifically to cancer cells.

MeSH terms

  • Antigens, Neoplasm
  • Cell Line, Tumor
  • Docetaxel
  • Humans
  • Nanoparticles*
  • Receptors, Antigen, T-Cell*
  • T-Lymphocytes

Substances

  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell
  • Docetaxel