Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion...

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Authors: Valdivia Lara, Edgar Guillermo, Alonso Miguel, Daniel, Pérez Alenza, María De Los Dolores, Zimmermann, Anna Barbara Emilia, Schaafsma, Evelien, Kolling IV, Fred W., Barreno San Antolín, Lucía, Alonso Díez, Ángela, Beiss, Veronique, Affonso de Oliveira, Jessica Fernanda, Suárez Redondo, María, Fiering, Steven, Steinmetz, Nicole F., Vom Berg, Johannes, Peña Fernández, Laura Luisa, Arias Pulido, Hugo
Format: article
Publication Date:2023
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/104430
Online Access:https://hdl.handle.net/20.500.14352/104430
Access Level:Open access
Keyword:636.7.09:616-006
Canine mammary cancer
Intratumoral immunotherapy
Plant virus
Cowpea mosaic virus
Nanoparticles
Immune cells
Tumor microenvironment
Patient outcome
Veterinaria
3109 Ciencias Veterinarias
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oai_identifier_str oai:docta.ucm.es:20.500.14352/104430
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repository_id_str
spelling Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer PatientsValdivia Lara, Edgar GuillermoAlonso Miguel, DanielPérez Alenza, María De Los DoloresZimmermann, Anna Barbara EmiliaSchaafsma, EvelienKolling IV, Fred W.Barreno San Antolín, LucíaAlonso Díez, ÁngelaBeiss, VeroniqueAffonso de Oliveira, Jessica FernandaSuárez Redondo, MaríaFiering, StevenSteinmetz, Nicole F.Vom Berg, JohannesPeña Fernández, Laura LuisaArias Pulido, Hugo636.7.09:616-006Canine mammary cancerIntratumoral immunotherapyPlant virusCowpea mosaic virusNanoparticlesImmune cellsTumor microenvironmentPatient outcomeVeterinaria3109 Ciencias VeterinariasThe lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.MDPIUniversidad Complutense de Madrid20232023-09-0820232023-09-08journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/104430reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PGC2018-094516-B-I00 VACUNACION IN SITU DE CANCER MAMARIO CANINO CON NANOPARTICULAS "COWPEA MOSAIC VIRAL-LIKE" COMO MODELO PARA EL CANCER DE MAMA HUMANOopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1044302026-06-02T12:44:21Z
dc.title.none.fl_str_mv Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
title Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
spellingShingle Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
Valdivia Lara, Edgar Guillermo
636.7.09:616-006
Canine mammary cancer
Intratumoral immunotherapy
Plant virus
Cowpea mosaic virus
Nanoparticles
Immune cells
Tumor microenvironment
Patient outcome
Veterinaria
3109 Ciencias Veterinarias
title_short Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
title_full Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
title_fullStr Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
title_full_unstemmed Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
title_sort Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
dc.creator.none.fl_str_mv Valdivia Lara, Edgar Guillermo
Alonso Miguel, Daniel
Pérez Alenza, María De Los Dolores
Zimmermann, Anna Barbara Emilia
Schaafsma, Evelien
Kolling IV, Fred W.
Barreno San Antolín, Lucía
Alonso Díez, Ángela
Beiss, Veronique
Affonso de Oliveira, Jessica Fernanda
Suárez Redondo, María
Fiering, Steven
Steinmetz, Nicole F.
Vom Berg, Johannes
Peña Fernández, Laura Luisa
Arias Pulido, Hugo
author Valdivia Lara, Edgar Guillermo
author_facet Valdivia Lara, Edgar Guillermo
Alonso Miguel, Daniel
Pérez Alenza, María De Los Dolores
Zimmermann, Anna Barbara Emilia
Schaafsma, Evelien
Kolling IV, Fred W.
Barreno San Antolín, Lucía
Alonso Díez, Ángela
Beiss, Veronique
Affonso de Oliveira, Jessica Fernanda
Suárez Redondo, María
Fiering, Steven
Steinmetz, Nicole F.
Vom Berg, Johannes
Peña Fernández, Laura Luisa
Arias Pulido, Hugo
author_role author
author2 Alonso Miguel, Daniel
Pérez Alenza, María De Los Dolores
Zimmermann, Anna Barbara Emilia
Schaafsma, Evelien
Kolling IV, Fred W.
Barreno San Antolín, Lucía
Alonso Díez, Ángela
Beiss, Veronique
Affonso de Oliveira, Jessica Fernanda
Suárez Redondo, María
Fiering, Steven
Steinmetz, Nicole F.
Vom Berg, Johannes
Peña Fernández, Laura Luisa
Arias Pulido, Hugo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 636.7.09:616-006
Canine mammary cancer
Intratumoral immunotherapy
Plant virus
Cowpea mosaic virus
Nanoparticles
Immune cells
Tumor microenvironment
Patient outcome
Veterinaria
3109 Ciencias Veterinarias
topic 636.7.09:616-006
Canine mammary cancer
Intratumoral immunotherapy
Plant virus
Cowpea mosaic virus
Nanoparticles
Immune cells
Tumor microenvironment
Patient outcome
Veterinaria
3109 Ciencias Veterinarias
description The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-09-08
2023
2023-09-08
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/104430
url https://hdl.handle.net/20.500.14352/104430
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PGC2018-094516-B-I00 VACUNACION IN SITU DE CANCER MAMARIO CANINO CON NANOPARTICULAS "COWPEA MOSAIC VIRAL-LIKE" COMO MODELO PARA EL CANCER DE MAMA HUMANO
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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