Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy

Autores
Labrada, Mayrel; Clavell, Marilyn; Bebelagua, Yanín; De León, Joel; Alonso, Daniel Fernando; Gabri, Mariano Rolando; Veloso, Roberto C; Vérez, Vicente; Fernández, Luis E.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
OBJECTIVE: The target concept means not only an aberrant expression of a particular molecule in tumour tissues but also evidence of a clear therapeutic advantage, as a consequence of immune-intervention, in an antigen-positive relevant tumour model. Since we reported the presence of NGcGM3 ganglioside in human breast tumours years ago and though Phase I clinical trials of a ganglioside containing vaccine have been conducted, a definitive direct validation of this peculiar molecule as target for cancer immunotherapy has remained unperformed. METHODS: Two animal models were used: leghorn chickens and C57BL/6 mice. The murine 3LL-D122 cell line, the derived subcutaneous tumours and metastatic lung lesions were processed for gangliosides identification. Active immunotherapy experiments in the 3LL-D122 spontaneous lung metastasis model were performed with NGcGM3/VSSP vaccine prepared by conjugation of NGcGM3 with the outer membrane proteins of Neisseria meningitides. RESULTS: The 3LL-D122 Lewis lung carcinoma results were consistent with an increased expression of NGcGM3 from primary tumours to metastatic lesions, as observed in human breast cancer samples. Both vaccines, prepared with synthetic or natural-source-derived ganglioside, showed similar anti-tumour and immunogenicity profiles. Finally, a clear involvement of NK1.1(+) cells and CD8(+) T cells in the anti-metastatic effect elicited by the vaccine was manifested. CONCLUSIONS: While 'proof of concept' Phase II and III clinical trials with the NGcGM3/VSSP vaccine in cancer patients are currently ongoing these results reasonably sustain the validation of this peculiar ganglioside as a novel target for cancer immunotherapy.
Fil: Labrada, Mayrel. Center of Molecular Immunology; Cuba
Fil: Clavell, Marilyn. Center of Molecular Immunology; Cuba
Fil: Bebelagua, Yanín. Center of Molecular Immunology; Cuba
Fil: De León, Joel. Center of Molecular Immunology; Cuba
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Veloso, Roberto C. Center of Molecular Immunology; Cuba
Fil: Vérez, Vicente. Center of Molecular Immunology; Cuba
Fil: Fernández, Luis E.. Center of Molecular Immunology; Cuba
Materia
Ganglioside
Immunotherapy
Cancer
Target
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:11336/102631
Acceder
id CONICETDig_2e51bcd09889534a38a3a294107fb93c
oai_identifier_str oai:ri.conicet.gov.ar:11336/102631
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapyLabrada, MayrelClavell, MarilynBebelagua, YanínDe León, JoelAlonso, Daniel FernandoGabri, Mariano RolandoVeloso, Roberto CVérez, VicenteFernández, Luis E.GangliosideImmunotherapyCancerTargethttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3OBJECTIVE: The target concept means not only an aberrant expression of a particular molecule in tumour tissues but also evidence of a clear therapeutic advantage, as a consequence of immune-intervention, in an antigen-positive relevant tumour model. Since we reported the presence of NGcGM3 ganglioside in human breast tumours years ago and though Phase I clinical trials of a ganglioside containing vaccine have been conducted, a definitive direct validation of this peculiar molecule as target for cancer immunotherapy has remained unperformed. METHODS: Two animal models were used: leghorn chickens and C57BL/6 mice. The murine 3LL-D122 cell line, the derived subcutaneous tumours and metastatic lung lesions were processed for gangliosides identification. Active immunotherapy experiments in the 3LL-D122 spontaneous lung metastasis model were performed with NGcGM3/VSSP vaccine prepared by conjugation of NGcGM3 with the outer membrane proteins of Neisseria meningitides. RESULTS: The 3LL-D122 Lewis lung carcinoma results were consistent with an increased expression of NGcGM3 from primary tumours to metastatic lesions, as observed in human breast cancer samples. Both vaccines, prepared with synthetic or natural-source-derived ganglioside, showed similar anti-tumour and immunogenicity profiles. Finally, a clear involvement of NK1.1(+) cells and CD8(+) T cells in the anti-metastatic effect elicited by the vaccine was manifested. CONCLUSIONS: While 'proof of concept' Phase II and III clinical trials with the NGcGM3/VSSP vaccine in cancer patients are currently ongoing these results reasonably sustain the validation of this peculiar ganglioside as a novel target for cancer immunotherapy.Fil: Labrada, Mayrel. Center of Molecular Immunology; CubaFil: Clavell, Marilyn. Center of Molecular Immunology; CubaFil: Bebelagua, Yanín. Center of Molecular Immunology; CubaFil: De León, Joel. Center of Molecular Immunology; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Veloso, Roberto C. Center of Molecular Immunology; CubaFil: Vérez, Vicente. Center of Molecular Immunology; CubaFil: Fernández, Luis E.. Center of Molecular Immunology; CubaInforma Healthcare2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/102631Labrada, Mayrel; Clavell, Marilyn; Bebelagua, Yanín; De León, Joel; Alonso, Daniel Fernando; et al.; Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy; Informa Healthcare; Expert Opinion on Biological Therapy; 10; 2; 12-2009; 153-1621471-2598CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1517/14712590903443084info:eu-repo/semantics/altIdentifier/doi/10.1517/14712590903443084info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:26Zoai:ri.conicet.gov.ar:11336/102631instacron: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:34982025-09-03 09:55:27.245CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
title Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
spellingShingle Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
Labrada, Mayrel
Ganglioside
Immunotherapy
Cancer
Target
title_short Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
title_full Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
title_fullStr Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
title_full_unstemmed Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
title_sort Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
dc.creator.none.fl_str_mv Labrada, Mayrel
Clavell, Marilyn
Bebelagua, Yanín
De León, Joel
Alonso, Daniel Fernando
Gabri, Mariano Rolando
Veloso, Roberto C
Vérez, Vicente
Fernández, Luis E.
author Labrada, Mayrel
author_facet Labrada, Mayrel
Clavell, Marilyn
Bebelagua, Yanín
De León, Joel
Alonso, Daniel Fernando
Gabri, Mariano Rolando
Veloso, Roberto C
Vérez, Vicente
Fernández, Luis E.
author_role author
author2 Clavell, Marilyn
Bebelagua, Yanín
De León, Joel
Alonso, Daniel Fernando
Gabri, Mariano Rolando
Veloso, Roberto C
Vérez, Vicente
Fernández, Luis E.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ganglioside
Immunotherapy
Cancer
Target
topic Ganglioside
Immunotherapy
Cancer
Target
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv OBJECTIVE: The target concept means not only an aberrant expression of a particular molecule in tumour tissues but also evidence of a clear therapeutic advantage, as a consequence of immune-intervention, in an antigen-positive relevant tumour model. Since we reported the presence of NGcGM3 ganglioside in human breast tumours years ago and though Phase I clinical trials of a ganglioside containing vaccine have been conducted, a definitive direct validation of this peculiar molecule as target for cancer immunotherapy has remained unperformed. METHODS: Two animal models were used: leghorn chickens and C57BL/6 mice. The murine 3LL-D122 cell line, the derived subcutaneous tumours and metastatic lung lesions were processed for gangliosides identification. Active immunotherapy experiments in the 3LL-D122 spontaneous lung metastasis model were performed with NGcGM3/VSSP vaccine prepared by conjugation of NGcGM3 with the outer membrane proteins of Neisseria meningitides. RESULTS: The 3LL-D122 Lewis lung carcinoma results were consistent with an increased expression of NGcGM3 from primary tumours to metastatic lesions, as observed in human breast cancer samples. Both vaccines, prepared with synthetic or natural-source-derived ganglioside, showed similar anti-tumour and immunogenicity profiles. Finally, a clear involvement of NK1.1(+) cells and CD8(+) T cells in the anti-metastatic effect elicited by the vaccine was manifested. CONCLUSIONS: While 'proof of concept' Phase II and III clinical trials with the NGcGM3/VSSP vaccine in cancer patients are currently ongoing these results reasonably sustain the validation of this peculiar ganglioside as a novel target for cancer immunotherapy.
Fil: Labrada, Mayrel. Center of Molecular Immunology; Cuba
Fil: Clavell, Marilyn. Center of Molecular Immunology; Cuba
Fil: Bebelagua, Yanín. Center of Molecular Immunology; Cuba
Fil: De León, Joel. Center of Molecular Immunology; Cuba
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Veloso, Roberto C. Center of Molecular Immunology; Cuba
Fil: Vérez, Vicente. Center of Molecular Immunology; Cuba
Fil: Fernández, Luis E.. Center of Molecular Immunology; Cuba
description OBJECTIVE: The target concept means not only an aberrant expression of a particular molecule in tumour tissues but also evidence of a clear therapeutic advantage, as a consequence of immune-intervention, in an antigen-positive relevant tumour model. Since we reported the presence of NGcGM3 ganglioside in human breast tumours years ago and though Phase I clinical trials of a ganglioside containing vaccine have been conducted, a definitive direct validation of this peculiar molecule as target for cancer immunotherapy has remained unperformed. METHODS: Two animal models were used: leghorn chickens and C57BL/6 mice. The murine 3LL-D122 cell line, the derived subcutaneous tumours and metastatic lung lesions were processed for gangliosides identification. Active immunotherapy experiments in the 3LL-D122 spontaneous lung metastasis model were performed with NGcGM3/VSSP vaccine prepared by conjugation of NGcGM3 with the outer membrane proteins of Neisseria meningitides. RESULTS: The 3LL-D122 Lewis lung carcinoma results were consistent with an increased expression of NGcGM3 from primary tumours to metastatic lesions, as observed in human breast cancer samples. Both vaccines, prepared with synthetic or natural-source-derived ganglioside, showed similar anti-tumour and immunogenicity profiles. Finally, a clear involvement of NK1.1(+) cells and CD8(+) T cells in the anti-metastatic effect elicited by the vaccine was manifested. CONCLUSIONS: While 'proof of concept' Phase II and III clinical trials with the NGcGM3/VSSP vaccine in cancer patients are currently ongoing these results reasonably sustain the validation of this peculiar ganglioside as a novel target for cancer immunotherapy.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
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/11336/102631
Labrada, Mayrel; Clavell, Marilyn; Bebelagua, Yanín; De León, Joel; Alonso, Daniel Fernando; et al.; Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy; Informa Healthcare; Expert Opinion on Biological Therapy; 10; 2; 12-2009; 153-162
1471-2598
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102631
identifier_str_mv Labrada, Mayrel; Clavell, Marilyn; Bebelagua, Yanín; De León, Joel; Alonso, Daniel Fernando; et al.; Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy; Informa Healthcare; Expert Opinion on Biological Therapy; 10; 2; 12-2009; 153-162
1471-2598
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1517/14712590903443084
info:eu-repo/semantics/altIdentifier/doi/10.1517/14712590903443084
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
application/pdf
dc.publisher.none.fl_str_mv Informa Healthcare
publisher.none.fl_str_mv Informa Healthcare
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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score 13.13397

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