Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma

Autores
Cocozza, Federico; Menay, Florencia; Tsacalian, Rodrigo Farid; Elisei, Analia; Sampedro, Pura; Soria, Ivana; Waldner, Claudia Inés; Gravisaco, María José; Mongini, Claudia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic drugs, hypoxia, acidosis, or radiation by increasing the release of EVs. In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly increased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, and CD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolated from LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cells were induced in immunized mice and a specific cytotoxic cellular immune response was elicited in vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs. Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhance the secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may be used to produce antigens for future design of cancer vaccines.
Instituto de Virología
Fil: Cocozza, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Menay, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Tsacalian, Rodrigo Farid. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Elisei, Analia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Sampedro, Pura. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina
Fil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Waldner, Claudia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina
Fuente
Vaccine 37 (12) : 1565-1576. (14 March 2019)
Materia
Ciclofosfamida
Neoplasmas
Respuesta Inmunológica
Linfoma
Vacuna
Linfocitos-t
Cyclophosphamide
Neoplasms
Immune Response
Lymphoma
Vaccines
T-lymphocytes
Extracellular Vesicles
Exosomes
Vesículas Extracelulares
Exosomas
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
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Acceder
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network_name_str INTA Digital (INTA)
spelling Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphomaCocozza, FedericoMenay, FlorenciaTsacalian, Rodrigo FaridElisei, AnaliaSampedro, PuraSoria, IvanaWaldner, Claudia InésGravisaco, María JoséMongini, ClaudiaCiclofosfamidaNeoplasmasRespuesta InmunológicaLinfomaVacunaLinfocitos-tCyclophosphamideNeoplasmsImmune ResponseLymphomaVaccinesT-lymphocytesExtracellular VesiclesExosomesVesículas ExtracelularesExosomasExosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic drugs, hypoxia, acidosis, or radiation by increasing the release of EVs. In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly increased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, and CD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolated from LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cells were induced in immunized mice and a specific cytotoxic cellular immune response was elicited in vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs. Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhance the secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may be used to produce antigens for future design of cancer vaccines.Instituto de VirologíaFil: Cocozza, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Menay, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Tsacalian, Rodrigo Farid. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Elisei, Analia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Sampedro, Pura. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Waldner, Claudia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaElsevier2019-03-13T13:08:41Z2019-03-13T13:08:41Z2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/4586https://www.sciencedirect.com/science/article/pii/S0264410X19301872?via%3Dihub0264-410Xhttps://doi.org/10.1016/j.vaccine.2019.02.004Vaccine 37 (12) : 1565-1576. 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dc.title.none.fl_str_mv Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
title Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
spellingShingle Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
Cocozza, Federico
Ciclofosfamida
Neoplasmas
Respuesta Inmunológica
Linfoma
Vacuna
Linfocitos-t
Cyclophosphamide
Neoplasms
Immune Response
Lymphoma
Vaccines
T-lymphocytes
Extracellular Vesicles
Exosomes
Vesículas Extracelulares
Exosomas
title_short Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
title_full Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
title_fullStr Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
title_full_unstemmed Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
title_sort Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
dc.creator.none.fl_str_mv Cocozza, Federico
Menay, Florencia
Tsacalian, Rodrigo Farid
Elisei, Analia
Sampedro, Pura
Soria, Ivana
Waldner, Claudia Inés
Gravisaco, María José
Mongini, Claudia
author Cocozza, Federico
author_facet Cocozza, Federico
Menay, Florencia
Tsacalian, Rodrigo Farid
Elisei, Analia
Sampedro, Pura
Soria, Ivana
Waldner, Claudia Inés
Gravisaco, María José
Mongini, Claudia
author_role author
author2 Menay, Florencia
Tsacalian, Rodrigo Farid
Elisei, Analia
Sampedro, Pura
Soria, Ivana
Waldner, Claudia Inés
Gravisaco, María José
Mongini, Claudia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciclofosfamida
Neoplasmas
Respuesta Inmunológica
Linfoma
Vacuna
Linfocitos-t
Cyclophosphamide
Neoplasms
Immune Response
Lymphoma
Vaccines
T-lymphocytes
Extracellular Vesicles
Exosomes
Vesículas Extracelulares
Exosomas
topic Ciclofosfamida
Neoplasmas
Respuesta Inmunológica
Linfoma
Vacuna
Linfocitos-t
Cyclophosphamide
Neoplasms
Immune Response
Lymphoma
Vaccines
T-lymphocytes
Extracellular Vesicles
Exosomes
Vesículas Extracelulares
Exosomas
dc.description.none.fl_txt_mv Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic drugs, hypoxia, acidosis, or radiation by increasing the release of EVs. In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly increased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, and CD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolated from LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cells were induced in immunized mice and a specific cytotoxic cellular immune response was elicited in vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs. Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhance the secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may be used to produce antigens for future design of cancer vaccines.
Instituto de Virología
Fil: Cocozza, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Menay, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Tsacalian, Rodrigo Farid. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Elisei, Analia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Sampedro, Pura. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina
Fil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Waldner, Claudia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina
description Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic drugs, hypoxia, acidosis, or radiation by increasing the release of EVs. In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly increased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, and CD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolated from LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cells were induced in immunized mice and a specific cytotoxic cellular immune response was elicited in vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs. Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhance the secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may be used to produce antigens for future design of cancer vaccines.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-13T13:08:41Z
2019-03-13T13:08:41Z
2019-03
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/20.500.12123/4586
https://www.sciencedirect.com/science/article/pii/S0264410X19301872?via%3Dihub
0264-410X
https://doi.org/10.1016/j.vaccine.2019.02.004
url http://hdl.handle.net/20.500.12123/4586
https://www.sciencedirect.com/science/article/pii/S0264410X19301872?via%3Dihub
https://doi.org/10.1016/j.vaccine.2019.02.004
identifier_str_mv 0264-410X
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
eu_rights_str_mv restrictedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Vaccine 37 (12) : 1565-1576. (14 March 2019)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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score 12.712165

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