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Abstract:

As cutaneous melanoma (CM) currently remains with a bleak prognosis, thorough investigation of new treatment options are of utmost relevance. In the phase II/III randomized clinical trial (CASVAC-0401), the repeated immunization of stages IIB-III CM patients with the irradiated, allogeneic cellular CSF-470 vaccine plus the adjuvants bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) demonstrated a significant benefit over IFN-alpha2B treatment in distant metastasis-free survival. Here we present on the short and long term immune monitoring results after completing the 2-year protocol; a continuation of the previous report by Mordoh et al. (1). We demonstrate that the repeated CSF-470 vaccinations stimulated a long term cellular and humoral immunity response directed against the vaccine antigens. In the case of 2 patients, we are able to show that a similar immune response was generated against autologous antigens. Evaluation of inhibitory receptor co-expression on patient's T cells indicates that the vaccination protocol did not stimulate T cell exhaustion. In order to better understand the basis for the efficacious vaccine responses observed, we investigated the short term immune events following vaccine injection. A significant increase in C-reactive protein (CRP) and IL-6 was observed 24 h after vaccination, with in vitro studies suggesting IL-6 production occurs in the vaccine site. We demonstrate that CRP enhances the cytotoxicity of peripheral blood mononuclear cells (PBMC) against melanoma cells in an in vitro model. Additionally, CRP stimulates the release of pro and anti-inflammatory cytokines from PBMC. As our results demonstrate that successive vaccinations with CSF-470 plus adjuvants promoted an increase in both anti-tumor innate and adaptive immunity, we propose a subsequent model of action. Copyright © 2018 Pampena, Cartar, Cueto, Levy, Blanco, Barrio and Mordoh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Registro:

Documento: Artículo
Título:Adjuvants in cutaneous melanoma patients: Long term antitumor immunity and short term release of acute inflammatory reactants
Autor:Pampena, M.B.; Cartar, H.C.; Cueto, G.R.; Levy, E.M.; Blanco, P.A.; Barrio, M.M.; Mordoh, J.
Filiación:Centro de Investigaciones Oncológicas-Fundación Cáncer, Buenos Aires, Argentina
Grupo de Bioestadística Aplicada, Departamento de Ecología, Genética y Evolución, Instituto de Ecología, Genética y Evolución de Buenos Aires (IEGEBA-UBA/CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Biotherapy, Instituto Alexander Fleming, Buenos Aires, Argentina
Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, Argentina
Palabras clave:Adaptive immunity; C-reactive protein; CSF-470 allogeneic cell vaccine; Cutaneous melanoma; Innate immunity; gamma interferon; granulocyte macrophage colony stimulating factor; antineoplastic activity; Article; cutaneous melanoma; enzyme linked immunosorbent assay; enzyme linked immunospot assay; fluorescence activated cell sorting; human; immune response; immunostimulation; peripheral blood mononuclear cell
Año:2018
Volumen:9
Número:NOV
DOI: http://dx.doi.org/10.3389/fimmu.2018.02531
Título revista:Frontiers in Immunology
Título revista abreviado:Front. Immunol.
ISSN:16643224
CAS:gamma interferon, 82115-62-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16643224_v9_nNOV_p_Pampena

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Citas:

---------- APA ----------
Pampena, M.B., Cartar, H.C., Cueto, G.R., Levy, E.M., Blanco, P.A., Barrio, M.M. & Mordoh, J. (2018) . Adjuvants in cutaneous melanoma patients: Long term antitumor immunity and short term release of acute inflammatory reactants. Frontiers in Immunology, 9(NOV).
http://dx.doi.org/10.3389/fimmu.2018.02531
---------- CHICAGO ----------
Pampena, M.B., Cartar, H.C., Cueto, G.R., Levy, E.M., Blanco, P.A., Barrio, M.M., et al. "Adjuvants in cutaneous melanoma patients: Long term antitumor immunity and short term release of acute inflammatory reactants" . Frontiers in Immunology 9, no. NOV (2018).
http://dx.doi.org/10.3389/fimmu.2018.02531
---------- MLA ----------
Pampena, M.B., Cartar, H.C., Cueto, G.R., Levy, E.M., Blanco, P.A., Barrio, M.M., et al. "Adjuvants in cutaneous melanoma patients: Long term antitumor immunity and short term release of acute inflammatory reactants" . Frontiers in Immunology, vol. 9, no. NOV, 2018.
http://dx.doi.org/10.3389/fimmu.2018.02531
---------- VANCOUVER ----------
Pampena, M.B., Cartar, H.C., Cueto, G.R., Levy, E.M., Blanco, P.A., Barrio, M.M., et al. Adjuvants in cutaneous melanoma patients: Long term antitumor immunity and short term release of acute inflammatory reactants. Front. Immunol. 2018;9(NOV).
http://dx.doi.org/10.3389/fimmu.2018.02531