Oncotarget

Research Papers:

Exceptional antineoplastic activity of a dendritic-cell-targeted vaccine loaded with a Listeria peptide proposed against metastatic melanoma

Ricardo Calderon-Gonzalez, Lucia Bronchalo-Vicente, Javier Freire, Elisabet Frande-Cabanes, Lidia Alaez-Alvarez, Javier Gomez-Roman, Sonsóles Yañez-Diaz and Carmen Alvarez-Dominguez _

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Oncotarget. 2016; 7:16855-16865. https://doi.org/10.18632/oncotarget.7806

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Abstract

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

Correspondence to:

Carmen Alvarez-Dominguez, e-mail: calvarez@humv.es

Keywords: dendritic cells, Listeria peptides, vaccines, melanoma, immunotherapy

Received: July 13, 2015     Accepted: February 09, 2016     Published: March 01, 2016

ABSTRACT

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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