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

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    Authors
    McDaid, William J
    Lissin, N.
    Pollheimer, E.
    Greene, M.
    Leach, A.
    Smyth, P.
    Bossi, G.
    Longley, D.
    Cole, D. K.
    Scott, C. J.
    Affiliation
    The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK, BT9 7AE
    Issue Date
    2021
    
    Metadata
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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.
    Citation
    McDaid WJ, Lissin N, Pollheimer E, Greene M, Leach A, Smyth P, et al. Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors. Nanoscale. 2021;13(35):15010–20.
    Journal
    Nanoscale
    URI
    http://hdl.handle.net/10541/624641
    DOI
    10.1039/d1nr04001d
    PubMed ID
    34533174
    Additional Links
    https://dx.doi.org/10.1039/d1nr04001d
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1039/d1nr04001d
    Scopus Count
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    All Paterson Institute for Cancer Research

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