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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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/104430
Acceso en línea:https://hdl.handle.net/20.500.14352/104430
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario: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.

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