Abstract:
:Anti-tumor immunity is limited by a number of factors including the lack of fully activated T-cells, insufficient antigenic stimulation and the immune-suppressive tumor microenvironment. We addressed these hurdles by developing a novel class of immunoconjugates, Antibody-Targeted Pathogen-derived Peptides (ATPPs), which were designed to efficiently deliver viral T-cell epitopes to tumors with the aim of redirecting virus-specific memory T-cells against the tumor. ATPPs were generated through covalent binding of mature MHC class I peptides to antibodies specific for cell surface-expressed tumor antigens that mediate immunoconjugate internalization. By means of a cleavable linker, the peptides are released in the endosomal compartment, from which they are loaded into MHC class I without the need for further processing. Pulsing of tumor cells with ATPPs was found to sensitize these for recognition by virus-specific CD8+ T-cells with much greater efficiency than exogenous loading with free peptides. Systemic injection of ATPPs into tumor-bearing mice enhanced the recruitment of virus-specific T-cells into the tumor and, when combined with immune checkpoint blockade, suppressed tumor growth. Our data thereby demonstrate the potential of ATPPs as a means of kick-starting the immune response against "cold" tumors and increasing the efficacy of checkpoint inhibitors.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Sefrin JP,Hillringhaus L,Mundigl O,Mann K,Ziegler-Landesberger D,Seul H,Tabares G,Knoblauch D,Leinenbach A,Friligou I,Dziadek S,Offringa R,Lifke V,Lifke Adoi
10.3389/fimmu.2019.01962subject
Has Abstractpub_date
2019-08-21 00:00:00pages
1962issn
1664-3224journal_volume
10pub_type
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journal_title:Frontiers in immunology
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,已发布勘误
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00151
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
pub_type: 杂志文章,meta分析
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pub_type: 杂志文章
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