Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer

Autores
Segatori, Valeria Inés; Rojo, Selene; Gulino, Cynthia Antonella; Capobianco, Carla Sabrina; Ferreira, Gretel Magalí; Crispo, Martina; Demarco, Ignacio A.; Spitzer, Eduardo; Gabri, Mariano Rolando; Alonso, Daniel Fernando
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death. Treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy, such as anti-programmed death-1 (PD-1) monoclonal antibody (mAb) pembrolizumab. Combining anti-PD-1 therapy with other active immunotherapies is an interesting option for improving patient outcomes. Racotumomab, an anti-idiotype mAb used as switch maintenance therapy in advanced NSCLC, enhances immune responses against N-glycolylneuraminic acid (NeuGc)-containing neoantigens. This study aims to assess the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a preclinical mouse model of NSCLC.Methods: In the present study, we assessed the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a Lewis lung carcinoma (LLC) mouse model, employing two treatment schedules. Syngeneic C57BL/6 mice were injected intravenously with LLC cells and treated with 1-2 doses of anti-PD-1 mAb [200 µg, intraperitoneal (IP)] and/or three weekly doses of racotumomab [200 µg, subcutaneous (SC)].Results: Although concurrent treatment did not improve the effect of monotherapies, sequential treatment with anti-PD-1 followed by racotumomab immunization produced a significantly higher reduction in lung nodule formation. Additionally, we demonstrated a significant association between dietary incorporation of exogenous NeuGc and the antitumor activity of racotumomab using a humanized NeuGc-negative mouse model that lacks the key enzyme necessary for NeuGc synthesis.Conclusions: Our preclinical data strongly support the efficacy of a sequential combination of PD-1 checkpoint blockade therapy and active vaccine immunotherapy racotumomab in the treatment of advanced NSCLC.
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Rojo, Selene. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Ferreira, Gretel Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Crispo, Martina. Instituto Pasteur de Montevideo; Uruguay
Fil: Demarco, Ignacio A.. Mabxience Sau.; Argentina
Fil: Spitzer, Eduardo. Elea-Phoenix Laboratories; 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: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Materia
N-glycolyl
(NeuGc) deficient mice
Racotumomab
Immune checkpoint blockade
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/283620
Acceder
id CONICETDig_358451029e5c3c3a62152add2a8d3231
oai_identifier_str oai:ri.conicet.gov.ar:11336/283620
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancerSegatori, Valeria InésRojo, SeleneGulino, Cynthia AntonellaCapobianco, Carla SabrinaFerreira, Gretel MagalíCrispo, MartinaDemarco, Ignacio A.Spitzer, EduardoGabri, Mariano RolandoAlonso, Daniel FernandoN-glycolyl(NeuGc) deficient miceRacotumomabImmune checkpoint blockadehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death. Treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy, such as anti-programmed death-1 (PD-1) monoclonal antibody (mAb) pembrolizumab. Combining anti-PD-1 therapy with other active immunotherapies is an interesting option for improving patient outcomes. Racotumomab, an anti-idiotype mAb used as switch maintenance therapy in advanced NSCLC, enhances immune responses against N-glycolylneuraminic acid (NeuGc)-containing neoantigens. This study aims to assess the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a preclinical mouse model of NSCLC.Methods: In the present study, we assessed the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a Lewis lung carcinoma (LLC) mouse model, employing two treatment schedules. Syngeneic C57BL/6 mice were injected intravenously with LLC cells and treated with 1-2 doses of anti-PD-1 mAb [200 µg, intraperitoneal (IP)] and/or three weekly doses of racotumomab [200 µg, subcutaneous (SC)].Results: Although concurrent treatment did not improve the effect of monotherapies, sequential treatment with anti-PD-1 followed by racotumomab immunization produced a significantly higher reduction in lung nodule formation. Additionally, we demonstrated a significant association between dietary incorporation of exogenous NeuGc and the antitumor activity of racotumomab using a humanized NeuGc-negative mouse model that lacks the key enzyme necessary for NeuGc synthesis.Conclusions: Our preclinical data strongly support the efficacy of a sequential combination of PD-1 checkpoint blockade therapy and active vaccine immunotherapy racotumomab in the treatment of advanced NSCLC.Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Rojo, Selene. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Ferreira, Gretel Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Crispo, Martina. Instituto Pasteur de Montevideo; UruguayFil: Demarco, Ignacio A.. Mabxience Sau.; ArgentinaFil: Spitzer, Eduardo. Elea-Phoenix Laboratories; 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: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaAME Publishing Company2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/283620Segatori, Valeria Inés; Rojo, Selene; Gulino, Cynthia Antonella; Capobianco, Carla Sabrina; Ferreira, Gretel Magalí; et al.; Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer; AME Publishing Company; Translational Lung Cancer Research; 14; 9; 9-2025; 3607-36222218-67512226-4477CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://tlcr.amegroups.org/article/view/106009/htmlinfo:eu-repo/semantics/altIdentifier/doi/10.21037/tlcr-2025-230info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:31:04Zoai:ri.conicet.gov.ar:11336/283620instacron: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:34982026-08-25 14:31:04.889CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
title Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
spellingShingle Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
Segatori, Valeria Inés
N-glycolyl
(NeuGc) deficient mice
Racotumomab
Immune checkpoint blockade
title_short Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
title_full Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
title_fullStr Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
title_full_unstemmed Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
title_sort Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer
dc.creator.none.fl_str_mv Segatori, Valeria Inés
Rojo, Selene
Gulino, Cynthia Antonella
Capobianco, Carla Sabrina
Ferreira, Gretel Magalí
Crispo, Martina
Demarco, Ignacio A.
Spitzer, Eduardo
Gabri, Mariano Rolando
Alonso, Daniel Fernando
author Segatori, Valeria Inés
author_facet Segatori, Valeria Inés
Rojo, Selene
Gulino, Cynthia Antonella
Capobianco, Carla Sabrina
Ferreira, Gretel Magalí
Crispo, Martina
Demarco, Ignacio A.
Spitzer, Eduardo
Gabri, Mariano Rolando
Alonso, Daniel Fernando
author_role author
author2 Rojo, Selene
Gulino, Cynthia Antonella
Capobianco, Carla Sabrina
Ferreira, Gretel Magalí
Crispo, Martina
Demarco, Ignacio A.
Spitzer, Eduardo
Gabri, Mariano Rolando
Alonso, Daniel Fernando
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv N-glycolyl
(NeuGc) deficient mice
Racotumomab
Immune checkpoint blockade
topic N-glycolyl
(NeuGc) deficient mice
Racotumomab
Immune checkpoint blockade
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death. Treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy, such as anti-programmed death-1 (PD-1) monoclonal antibody (mAb) pembrolizumab. Combining anti-PD-1 therapy with other active immunotherapies is an interesting option for improving patient outcomes. Racotumomab, an anti-idiotype mAb used as switch maintenance therapy in advanced NSCLC, enhances immune responses against N-glycolylneuraminic acid (NeuGc)-containing neoantigens. This study aims to assess the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a preclinical mouse model of NSCLC.Methods: In the present study, we assessed the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a Lewis lung carcinoma (LLC) mouse model, employing two treatment schedules. Syngeneic C57BL/6 mice were injected intravenously with LLC cells and treated with 1-2 doses of anti-PD-1 mAb [200 µg, intraperitoneal (IP)] and/or three weekly doses of racotumomab [200 µg, subcutaneous (SC)].Results: Although concurrent treatment did not improve the effect of monotherapies, sequential treatment with anti-PD-1 followed by racotumomab immunization produced a significantly higher reduction in lung nodule formation. Additionally, we demonstrated a significant association between dietary incorporation of exogenous NeuGc and the antitumor activity of racotumomab using a humanized NeuGc-negative mouse model that lacks the key enzyme necessary for NeuGc synthesis.Conclusions: Our preclinical data strongly support the efficacy of a sequential combination of PD-1 checkpoint blockade therapy and active vaccine immunotherapy racotumomab in the treatment of advanced NSCLC.
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Rojo, Selene. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Ferreira, Gretel Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Crispo, Martina. Instituto Pasteur de Montevideo; Uruguay
Fil: Demarco, Ignacio A.. Mabxience Sau.; Argentina
Fil: Spitzer, Eduardo. Elea-Phoenix Laboratories; 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: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
description Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death. Treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy, such as anti-programmed death-1 (PD-1) monoclonal antibody (mAb) pembrolizumab. Combining anti-PD-1 therapy with other active immunotherapies is an interesting option for improving patient outcomes. Racotumomab, an anti-idiotype mAb used as switch maintenance therapy in advanced NSCLC, enhances immune responses against N-glycolylneuraminic acid (NeuGc)-containing neoantigens. This study aims to assess the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a preclinical mouse model of NSCLC.Methods: In the present study, we assessed the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a Lewis lung carcinoma (LLC) mouse model, employing two treatment schedules. Syngeneic C57BL/6 mice were injected intravenously with LLC cells and treated with 1-2 doses of anti-PD-1 mAb [200 µg, intraperitoneal (IP)] and/or three weekly doses of racotumomab [200 µg, subcutaneous (SC)].Results: Although concurrent treatment did not improve the effect of monotherapies, sequential treatment with anti-PD-1 followed by racotumomab immunization produced a significantly higher reduction in lung nodule formation. Additionally, we demonstrated a significant association between dietary incorporation of exogenous NeuGc and the antitumor activity of racotumomab using a humanized NeuGc-negative mouse model that lacks the key enzyme necessary for NeuGc synthesis.Conclusions: Our preclinical data strongly support the efficacy of a sequential combination of PD-1 checkpoint blockade therapy and active vaccine immunotherapy racotumomab in the treatment of advanced NSCLC.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
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/11336/283620
Segatori, Valeria Inés; Rojo, Selene; Gulino, Cynthia Antonella; Capobianco, Carla Sabrina; Ferreira, Gretel Magalí; et al.; Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer; AME Publishing Company; Translational Lung Cancer Research; 14; 9; 9-2025; 3607-3622
2218-6751
2226-4477
CONICET Digital
CONICET
url http://hdl.handle.net/11336/283620
identifier_str_mv Segatori, Valeria Inés; Rojo, Selene; Gulino, Cynthia Antonella; Capobianco, Carla Sabrina; Ferreira, Gretel Magalí; et al.; Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer; AME Publishing Company; Translational Lung Cancer Research; 14; 9; 9-2025; 3607-3622
2218-6751
2226-4477
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://tlcr.amegroups.org/article/view/106009/html
info:eu-repo/semantics/altIdentifier/doi/10.21037/tlcr-2025-230
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv AME Publishing Company
publisher.none.fl_str_mv AME Publishing Company
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
_version_ 1874774050596716544
score 13.24418

Publicaciones similares