| Title: |
Intratumoral neoadjuvant immunotherapy based on the BO-112 viral RNA mimetic |
| Authors: |
Álvarez, M. (Maite); Molina, C. (Carmen); Garasa, S. (Saray); Ochoa, M.C. (María Carmen); Rodriguez-Ruiz, M.E. (María Esperanza); Gomis, G. (Gabriel); Cirella, A. (Assunta); Olivera, I. (Irene); Glez-Vaz, J. (Javier); González-Gomariz, J. (José); Luri-Rey, C. (Carlos); Azpilikueta, A. (Arantza); Bolaños, E. (Elixabet); Teijeira, A. (Álvaro); Berraondo, P. (Pedro); Quintero, M. (Marisol); Melero, I. (Ignacio) |
| Publication Year: |
2023 |
| Collection: |
dadun - Depósito Académico Digital Universidad de Navarra |
| Subject Terms: |
Neoadjuvant; BO-112; PD-1; Metastases; Intratumoral immunotherapy |
| Description: |
BO-112 is a poly I:C-based viral mimetic that exerts anti-tumor efficacy when intratumorally delivered in mouse models. Intratumoral BO-112 synergizes in mice with systemic anti-PD-1 mAbs and this combination has attained efficacy in PD1-refractory melanoma patients. We sought to evaluate the anti-tumor efficacy of BO-112 pre-surgically applied in neoadjuvant settings to mouse models. We have observed that repeated intratumoral injections of BO-112 prior to surgical excision of the primary tumor significantly reduced tumor metastasis from orthotopically implanted 4T1-derived tumors and subcutaneous MC38-derived tumors in mice. Such effects were enhanced when combined with systemic anti-PD-1 mAb. The anti-tumor efficacy of this neoadjuvant immunotherapy approach depended on the presence of antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells. Since BO-112 has been successful in phase-two clinical trials for metastatic melanoma, these results provide a strong rationale for translating this pre-surgical strategy into clinical settings, especially in combination with standard-of-care checkpoint inhibitors. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PDC2021-121769-C21/ES/DESARROLO PRECLINICO Y TRANSLACIONAL DE UNA ESTRATEGIA INMUNOTERAPIA INTRATUMORAL CONSITENTE EN LA COMBINACION DE BO-112 Y AGONISTAS DE STING; info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F00147/ES/Resultados de investigación Proyectos Plataforma de cribado de moléculas inmunoestimulantes bifuncionales para tratamiento personalizado del cáncer renal; https://hdl.handle.net/10171/68037 |
| Availability: |
https://hdl.handle.net/10171/68037 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.25BFC660 |
| Database: |
BASE |