TY - JOUR
T1 - Exceptional antineoplastic activity of a dendritic-cell-targeted vaccine loaded with a Listeria peptide proposed against metastatic melanoma
AU - Calderon-Gonzalez, Ricardo
AU - Bronchalo-Vicente, Lucia
AU - Freire, Javier
AU - Frande-Cabanes, Elisabet
AU - Alaez-Alvarez, Lidia
AU - Gomez-Roman, Jose Javier
AU - Yañez-Diaz, Sonsoles
AU - Alvarez-Dominguez, Carmen
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Vaccination with dendritic cells (DCs) is proposed to induce lasting responses against melanoma but its survival benefit in patients needs to be demonstrated. We propose a DC-targeted vaccine loaded with a Listeria peptide with exceptional anti-tumour activity to prevent metastasis of melanoma. Mice vaccinated with vaccines based on DCs loaded with listeriolysin O peptide (91-99) (LLO91-99) showed clear reduction of metastatic B16OVA melanoma size and adhesion, prevention of lung metastasis, enhanced survival, and reversion of immune tolerance. Robust innate and specific immune responses explained the efficiency of DC-LLO91-99 vaccines against B16OVA melanoma. The noTable features of this vaccine related to melanoma reduction were: expansion of immune-dominant LLO91-99-specific CD8 T cells that helped to expand melanoma-specific CD8+ T cells; high numbers of tumour-infiltrating lymphocytes with a cytotoxic phenotype; and a decrease in CD4+CD25high regulatory T cells. This vaccine might be a useful alternative treatment for advanced melanoma, alone or in combination with other therapies.
AB - Vaccination with dendritic cells (DCs) is proposed to induce lasting responses against melanoma but its survival benefit in patients needs to be demonstrated. We propose a DC-targeted vaccine loaded with a Listeria peptide with exceptional anti-tumour activity to prevent metastasis of melanoma. Mice vaccinated with vaccines based on DCs loaded with listeriolysin O peptide (91-99) (LLO91-99) showed clear reduction of metastatic B16OVA melanoma size and adhesion, prevention of lung metastasis, enhanced survival, and reversion of immune tolerance. Robust innate and specific immune responses explained the efficiency of DC-LLO91-99 vaccines against B16OVA melanoma. The noTable features of this vaccine related to melanoma reduction were: expansion of immune-dominant LLO91-99-specific CD8 T cells that helped to expand melanoma-specific CD8+ T cells; high numbers of tumour-infiltrating lymphocytes with a cytotoxic phenotype; and a decrease in CD4+CD25high regulatory T cells. This vaccine might be a useful alternative treatment for advanced melanoma, alone or in combination with other therapies.
KW - Listeria peptides
KW - Dendritic cells
KW - Immunotherapy
KW - Melanoma
KW - Vaccines
U2 - 10.18632/oncotarget.7806
DO - 10.18632/oncotarget.7806
M3 - Article
VL - 7
SP - 16855
EP - 16865
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 13
ER -