Abstract
Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy. Interest in developing novel immunotherapies in HNSCC has been reawakened by the success of cetuximab, a therapeutic monoclonal antibody (mAb) against the epidermal growth factor receptor, which likely relies on immune as well as antisignaling mechanisms. This review focuses on novel therapeutic mAbs in current clinical development against established mechanisms of immune evasion in HNSCC, targeting: 1) tumor antigens, with resultant potential to induce antibody-dependent cell-mediated cytotoxicity and T cell activation; 2) immunosuppressive cytokines; 3) costimulatory tumor necrosis factor-family receptors; and 4) coinhibitory immune checkpoint receptors. Clinical trials of immunotherapeutic mAbs as monotherapy, in combination with cytolytic standard therapies exposing tumor antigens or in combination with other immunomodulatory mAbs, are urgently needed in HNSCC.
Keywords:
angiogenesis; antibodies; cytokines; growth factors; immune escape; immunity.
© 2013 American Cancer Society.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Antibodies, Monoclonal / immunology*
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use*
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Antibodies, Monoclonal, Humanized / immunology
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Antibodies, Monoclonal, Humanized / therapeutic use
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Antibody-Dependent Cell Cytotoxicity / drug effects
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Antibody-Dependent Cell Cytotoxicity / immunology
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Antigens, Neoplasm / drug effects
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Antineoplastic Agents / immunology*
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Carcinoma, Squamous Cell / drug therapy*
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Carcinoma, Squamous Cell / immunology*
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Cetuximab
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Cytokines / antagonists & inhibitors
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Head and Neck Neoplasms / drug therapy*
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Head and Neck Neoplasms / immunology*
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Humans
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Immunoglobulin G / drug effects
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Immunotherapy / methods
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Receptors, Tumor Necrosis Factor / antagonists & inhibitors
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Squamous Cell Carcinoma of Head and Neck
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antigens, Neoplasm
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Antineoplastic Agents
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Cytokines
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Immunoglobulin G
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Receptors, Tumor Necrosis Factor
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Cetuximab