vtx-2337 and Head-and-Neck-Neoplasms

vtx-2337 has been researched along with Head-and-Neck-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for vtx-2337 and Head-and-Neck-Neoplasms

Article	Year
TLR8 stimulation enhances cetuximab-mediated natural killer cell lysis of head and neck cancer cells and dendritic cell cross-priming of EGFR-specific CD8+ T cells. Cancer immunology, immunotherapy : CII, 2013, Volume: 62, Issue:8 Cetuximab is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody that prolongs survival in the treatment for head and neck cancer (HNC), but only in 10-20 % of patients. An immunological mechanism of action such as natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been suggested. We investigated the effects of activating toll-like receptor (TLR)-8 to enhance activity of cetuximab-stimulated, FcγR-bearing cells.. To determine the capability of TLR8-stimulation to enhance the activation and function of NK cells and dendritic cells (DC) in the presence of cetuximab-coated HNC cells.. Peripheral blood mononuclear cells (PBMC), NK, DC, and CD8(+) T cells were isolated and analyzed using (51)Cr release ADCC, flow cytometry analysis, cytokine ELISA, and EGFR853-861 tetramer staining.. TLR8 stimulation of unfractionated PBMC led to enhanced cetuximab-mediated ADCC in healthy donors (p < 0.01) and HNC patients (p < 0.001), which was dependent on NK cells. Secretion of Th1 cytokines TNFα (p < 0.0001), IFNγ (p < 0.0001), and IL-12p40 (p < 0.005) was increased. TLR8 stimulation of PBMC augmented cetuximab-enhanced NK cell degranulation (p < 0.001). TLR8-stimulated NK cells enhanced DC maturation markers CD80, CD83, and CD86 in co-culture with cetuximab-treated HNC cells. TLR8 stimulation of NK-DC co-cultures significantly increased DC priming of EGFR-specific CD8(+) T cells in the presence of cetuximab.. VTX-2337 and cetuximab combination therapy can activate innate and adaptive anti-cancer immune responses. Further investigation in human trials will be important for determining the clinical benefit of this combination and for determining biomarkers of response. Topics: Antibodies, Monoclonal, Humanized; Antibody-Dependent Cell Cytotoxicity; Antigens, CD; Antineoplastic Agents; B7-1 Antigen; B7-2 Antigen; Benzazepines; CD8-Positive T-Lymphocytes; CD83 Antigen; Cell Line, Tumor; Cells, Cultured; Cetuximab; Coculture Techniques; Cross-Priming; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; ErbB Receptors; Flow Cytometry; Head and Neck Neoplasms; Humans; Immunoglobulins; Interferon-gamma; Interleukin-12 Subunit p40; Killer Cells, Natural; Membrane Glycoproteins; Toll-Like Receptor 8; Tumor Necrosis Factor-alpha	2013

Article

Year

TLR8 stimulation enhances cetuximab-mediated natural killer cell lysis of head and neck cancer cells and dendritic cell cross-priming of EGFR-specific CD8+ T cells.

Cancer immunology, immunotherapy : CII, 2013, Volume: 62, Issue:8

Cetuximab is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody that prolongs survival in the treatment for head and neck cancer (HNC), but only in 10-20 % of patients. An immunological mechanism of action such as natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been suggested. We investigated the effects of activating toll-like receptor (TLR)-8 to enhance activity of cetuximab-stimulated, FcγR-bearing cells.. To determine the capability of TLR8-stimulation to enhance the activation and function of NK cells and dendritic cells (DC) in the presence of cetuximab-coated HNC cells.. Peripheral blood mononuclear cells (PBMC), NK, DC, and CD8(+) T cells were isolated and analyzed using (51)Cr release ADCC, flow cytometry analysis, cytokine ELISA, and EGFR853-861 tetramer staining.. TLR8 stimulation of unfractionated PBMC led to enhanced cetuximab-mediated ADCC in healthy donors (p < 0.01) and HNC patients (p < 0.001), which was dependent on NK cells. Secretion of Th1 cytokines TNFα (p < 0.0001), IFNγ (p < 0.0001), and IL-12p40 (p < 0.005) was increased. TLR8 stimulation of PBMC augmented cetuximab-enhanced NK cell degranulation (p < 0.001). TLR8-stimulated NK cells enhanced DC maturation markers CD80, CD83, and CD86 in co-culture with cetuximab-treated HNC cells. TLR8 stimulation of NK-DC co-cultures significantly increased DC priming of EGFR-specific CD8(+) T cells in the presence of cetuximab.. VTX-2337 and cetuximab combination therapy can activate innate and adaptive anti-cancer immune responses. Further investigation in human trials will be important for determining the clinical benefit of this combination and for determining biomarkers of response.

Topics: Antibodies, Monoclonal, Humanized; Antibody-Dependent Cell Cytotoxicity; Antigens, CD; Antineoplastic Agents; B7-1 Antigen; B7-2 Antigen; Benzazepines; CD8-Positive T-Lymphocytes; CD83 Antigen; Cell Line, Tumor; Cells, Cultured; Cetuximab; Coculture Techniques; Cross-Priming; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; ErbB Receptors; Flow Cytometry; Head and Neck Neoplasms; Humans; Immunoglobulins; Interferon-gamma; Interleukin-12 Subunit p40; Killer Cells, Natural; Membrane Glycoproteins; Toll-Like Receptor 8; Tumor Necrosis Factor-alpha

2013