Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors
Authors Name:
William J. McDaid, Nikolai Lissin, Ellen Pollheimer, Michelle Greene, Adam Leach, Peter Smyth, Giovanna Bossi, Daniel Longley, David K. Cole and Christopher J. Scott
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.
Journal:
DOI:
https://doi.org/10.1039/D1NR04001D
Publication date:
2021-08-20
Link to article (if provided):
Published on 2021-08-20