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

William J. McDaid, Nikolai Lissin, Ellen Pollheimer, Michelle Greene, Adam Leach, Peter Smyth, Giovanna Bossi, Daniel Longley, David K. Cole, Christopher J. Scott

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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.
Original languageEnglish
Pages (from-to)15010-15020
JournalNanoscale
Volume13
Issue number35
Early online date20 Aug 2021
DOIs
Publication statusEarly online date - 20 Aug 2021

Keywords

  • General Materials Science

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