Abstract
huHMFG-1 (AS1402) is a humanised IgG1 against MUC1, which exerts tumour cell killing through antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Here, we explored the capacity of invariant NKT (iNKT) cells, which are known to activate NK cells, and toll-like receptor (TLR) ligands which activate both iNKT and NK cells, to enhance huHMFG-1-ADCC. Addition of iNKT cells, as well as TLR2/6, 7, 8 and 9 agonists to PBMC improved the efficacy of huHMFG-1. These results suggest that transfer of ex vivo expanded iNKT cells or TLR agonist treatment may improve the efficacy of NK cell-mediated antibody-based tumour immunotherapies.
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / therapeutic use
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Antibody-Dependent Cell Cytotoxicity / immunology*
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Antigens, CD / immunology
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Antigens, Differentiation, T-Lymphocyte / immunology
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Flow Cytometry
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Granzymes / immunology
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Humans
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Immunoglobulin G / pharmacology*
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Immunotherapy / methods
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Killer Cells, Natural / immunology
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Lectins, C-Type
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Leukocytes, Mononuclear / immunology
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Lymphocyte Activation
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Mice
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Mucin-1 / immunology*
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Natural Killer T-Cells / immunology*
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Toll-Like Receptors / immunology*
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Immunoglobulin G
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Lectins, C-Type
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Mucin-1
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Toll-Like Receptors
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pemtumomab
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Granzymes