Exceptional antineoplastic activity of a dendritic-cell-targeted vaccine loaded with a Listeria peptide proposed against metastatic melanoma
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Ricardo Calderon-Gonzalez1, Lucia Bronchalo-Vicente1,2, Javier Freire3, Elisabet Frande-Cabanes1, Lidia Alaez-Alvarez1, Javier Gomez-Roman3, Sonsóles Yañez-Diaz2, Carmen Alvarez-Dominguez1
1Group of Genomics, Proteomics and Vaccines, Marqués de Valdecilla Research Institute (IDIVAL), Santander, Spain
2Dermatology Department, Marqués de Valdecilla University Hospital (HUMV), Santander, Spain
3Pathological Anatomy Department, Marqués de Valdecilla University Hospital (HUMV), Santander, Spain
Carmen Alvarez-Dominguez, e-mail: firstname.lastname@example.org
Keywords: dendritic cells, Listeria peptides, vaccines, melanoma, immunotherapy
Received: July 13, 2015 Accepted: February 09, 2016 Published: March 01, 2016
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.
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