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

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.

SUBMITTER: McDaid WJ

PROVIDER: S-EPMC8447836 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

McDaid William J WJ Lissin Nikolai N Pollheimer Ellen E Greene Michelle M Leach Adam A Smyth Peter P Bossi Giovanna G Longley Daniel D Cole David K DK Scott Christopher J CJ

Nanoscale 20210917 35

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 <i>via</i> T cell receptors (TCRs). In this study, docetaxel-loaded polymeric NPs were conjugated to recombinant affinity-enhanced TCRs to ...[more]

PMID: 34533174

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

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

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