Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release

Autores
Pampena, María Betina; Barrio, Maria Marcela; Juliá, Estefanía Paula; Blanco, Paula A.; Von Euw, Erika María; Mordoh, Jose; Levy, Estrella Mariel
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In a previous work, we showed that CSF-470 vaccine plus bacillus Calmette–Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs. IFN-α2b-treated high-risk cutaneous melanoma patients in a Phase II study. Immune monitoring demonstrated an increase in anti-tumor innate and adaptive immunities of vaccinated patients, with a striking increase in IFN-γ secreting lymphocytes specific for melanoma antigens (Ags). In an effort to dissect the first steps of the immune response elicited by CSF-470 vaccine plus adjuvants, we evaluated, in an in vitro model, leukocyte migration, cytokine production, and monocyte phagocytosis of vaccine cells. Our results demonstrate that leukocytes recruitment, mostly from the innate immune system, is an early event after CSF-470 vaccine plus BCG plus GM-CSF interaction with immune cells, possibly explained by the high expression of CCL2/MCP-1 and other chemokines by vaccine cells. Early release of TNF-α and IL-1β pro-inflammatory cytokines and efficient tumor Ags phagocytosis by monocytes take place and would probably create a favorable context for Ag processing and presentation. Although the presence of the vaccine cells hampered cytokines production stimulated by BCG in a mechanism partially mediated by TGF-β and IL-10, still significant levels of TNF-α and IL-1β could be detected. Thus, BCG was required to induce local inflammation in the presence of CSF-470 vaccine cells.
Fil: Pampena, María Betina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barrio, Maria Marcela. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Juliá, Estefanía Paula. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blanco, Paula A.. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Von Euw, Erika María. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mordoh, Jose. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Instituto Médico Especializado Alexander Fleming; Argentina
Fil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
ADJUVANTS
BACILLUS CALMETTE-GUERIN
IMMUNOTHERAPY
INNATE IMMUNITY
LEUKOCYTE RECRUITMENT
MELANOMA VACCINE
PRO-INFLAMMATORY CYTOKINES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/41331

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oai_identifier_str oai:ri.conicet.gov.ar:11336/41331
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine releasePampena, María BetinaBarrio, Maria MarcelaJuliá, Estefanía PaulaBlanco, Paula A.Von Euw, Erika MaríaMordoh, JoseLevy, Estrella MarielADJUVANTSBACILLUS CALMETTE-GUERINIMMUNOTHERAPYINNATE IMMUNITYLEUKOCYTE RECRUITMENTMELANOMA VACCINEPRO-INFLAMMATORY CYTOKINEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In a previous work, we showed that CSF-470 vaccine plus bacillus Calmette–Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs. IFN-α2b-treated high-risk cutaneous melanoma patients in a Phase II study. Immune monitoring demonstrated an increase in anti-tumor innate and adaptive immunities of vaccinated patients, with a striking increase in IFN-γ secreting lymphocytes specific for melanoma antigens (Ags). In an effort to dissect the first steps of the immune response elicited by CSF-470 vaccine plus adjuvants, we evaluated, in an in vitro model, leukocyte migration, cytokine production, and monocyte phagocytosis of vaccine cells. Our results demonstrate that leukocytes recruitment, mostly from the innate immune system, is an early event after CSF-470 vaccine plus BCG plus GM-CSF interaction with immune cells, possibly explained by the high expression of CCL2/MCP-1 and other chemokines by vaccine cells. Early release of TNF-α and IL-1β pro-inflammatory cytokines and efficient tumor Ags phagocytosis by monocytes take place and would probably create a favorable context for Ag processing and presentation. Although the presence of the vaccine cells hampered cytokines production stimulated by BCG in a mechanism partially mediated by TGF-β and IL-10, still significant levels of TNF-α and IL-1β could be detected. Thus, BCG was required to induce local inflammation in the presence of CSF-470 vaccine cells.Fil: Pampena, María Betina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barrio, Maria Marcela. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Juliá, Estefanía Paula. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blanco, Paula A.. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Von Euw, Erika María. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mordoh, Jose. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Instituto Médico Especializado Alexander Fleming; ArgentinaFil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFrontiers Research Foundation2017-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41331Pampena, María Betina; Barrio, Maria Marcela; Juliá, Estefanía Paula; Blanco, Paula A.; Von Euw, Erika María; et al.; Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release; Frontiers Research Foundation; Frontiers in Immunology; 8; OCT; 10-2017; 1-13; 13421664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2017.01342info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2017.01342/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:52Zoai:ri.conicet.gov.ar:11336/41331instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:23:52.916CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
title Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
spellingShingle Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
Pampena, María Betina
ADJUVANTS
BACILLUS CALMETTE-GUERIN
IMMUNOTHERAPY
INNATE IMMUNITY
LEUKOCYTE RECRUITMENT
MELANOMA VACCINE
PRO-INFLAMMATORY CYTOKINES
title_short Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
title_full Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
title_fullStr Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
title_full_unstemmed Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
title_sort Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release
dc.creator.none.fl_str_mv Pampena, María Betina
Barrio, Maria Marcela
Juliá, Estefanía Paula
Blanco, Paula A.
Von Euw, Erika María
Mordoh, Jose
Levy, Estrella Mariel
author Pampena, María Betina
author_facet Pampena, María Betina
Barrio, Maria Marcela
Juliá, Estefanía Paula
Blanco, Paula A.
Von Euw, Erika María
Mordoh, Jose
Levy, Estrella Mariel
author_role author
author2 Barrio, Maria Marcela
Juliá, Estefanía Paula
Blanco, Paula A.
Von Euw, Erika María
Mordoh, Jose
Levy, Estrella Mariel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ADJUVANTS
BACILLUS CALMETTE-GUERIN
IMMUNOTHERAPY
INNATE IMMUNITY
LEUKOCYTE RECRUITMENT
MELANOMA VACCINE
PRO-INFLAMMATORY CYTOKINES
topic ADJUVANTS
BACILLUS CALMETTE-GUERIN
IMMUNOTHERAPY
INNATE IMMUNITY
LEUKOCYTE RECRUITMENT
MELANOMA VACCINE
PRO-INFLAMMATORY CYTOKINES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In a previous work, we showed that CSF-470 vaccine plus bacillus Calmette–Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs. IFN-α2b-treated high-risk cutaneous melanoma patients in a Phase II study. Immune monitoring demonstrated an increase in anti-tumor innate and adaptive immunities of vaccinated patients, with a striking increase in IFN-γ secreting lymphocytes specific for melanoma antigens (Ags). In an effort to dissect the first steps of the immune response elicited by CSF-470 vaccine plus adjuvants, we evaluated, in an in vitro model, leukocyte migration, cytokine production, and monocyte phagocytosis of vaccine cells. Our results demonstrate that leukocytes recruitment, mostly from the innate immune system, is an early event after CSF-470 vaccine plus BCG plus GM-CSF interaction with immune cells, possibly explained by the high expression of CCL2/MCP-1 and other chemokines by vaccine cells. Early release of TNF-α and IL-1β pro-inflammatory cytokines and efficient tumor Ags phagocytosis by monocytes take place and would probably create a favorable context for Ag processing and presentation. Although the presence of the vaccine cells hampered cytokines production stimulated by BCG in a mechanism partially mediated by TGF-β and IL-10, still significant levels of TNF-α and IL-1β could be detected. Thus, BCG was required to induce local inflammation in the presence of CSF-470 vaccine cells.
Fil: Pampena, María Betina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barrio, Maria Marcela. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Juliá, Estefanía Paula. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blanco, Paula A.. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Von Euw, Erika María. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mordoh, Jose. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Instituto Médico Especializado Alexander Fleming; Argentina
Fil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description In a previous work, we showed that CSF-470 vaccine plus bacillus Calmette–Guerin (BCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) as adjuvants resulted in a significant benefit in the distant metastasis-free survival when comparing vaccinated vs. IFN-α2b-treated high-risk cutaneous melanoma patients in a Phase II study. Immune monitoring demonstrated an increase in anti-tumor innate and adaptive immunities of vaccinated patients, with a striking increase in IFN-γ secreting lymphocytes specific for melanoma antigens (Ags). In an effort to dissect the first steps of the immune response elicited by CSF-470 vaccine plus adjuvants, we evaluated, in an in vitro model, leukocyte migration, cytokine production, and monocyte phagocytosis of vaccine cells. Our results demonstrate that leukocytes recruitment, mostly from the innate immune system, is an early event after CSF-470 vaccine plus BCG plus GM-CSF interaction with immune cells, possibly explained by the high expression of CCL2/MCP-1 and other chemokines by vaccine cells. Early release of TNF-α and IL-1β pro-inflammatory cytokines and efficient tumor Ags phagocytosis by monocytes take place and would probably create a favorable context for Ag processing and presentation. Although the presence of the vaccine cells hampered cytokines production stimulated by BCG in a mechanism partially mediated by TGF-β and IL-10, still significant levels of TNF-α and IL-1β could be detected. Thus, BCG was required to induce local inflammation in the presence of CSF-470 vaccine cells.
publishDate 2017
dc.date.none.fl_str_mv 2017-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/41331
Pampena, María Betina; Barrio, Maria Marcela; Juliá, Estefanía Paula; Blanco, Paula A.; Von Euw, Erika María; et al.; Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release; Frontiers Research Foundation; Frontiers in Immunology; 8; OCT; 10-2017; 1-13; 1342
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41331
identifier_str_mv Pampena, María Betina; Barrio, Maria Marcela; Juliá, Estefanía Paula; Blanco, Paula A.; Von Euw, Erika María; et al.; Early events of the reaction elicited by CSF-470 melanoma vaccine plus adjuvants: An in vitro analysis of immune recruitment and cytokine release; Frontiers Research Foundation; Frontiers in Immunology; 8; OCT; 10-2017; 1-13; 1342
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2017.01342
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2017.01342/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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