Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem
Osteosarcoma is an aggressive bone tumor occurring primarily in pediatric patients. Despite years of intensive research, the outcomes of patients with metastatic disease or those who do not respond to therapy have remained poor and have not changed in the last 30 years. Oncolytic virotherapy is beco...
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/116490 |
| Acceso en línea: | https://hdl.handle.net/10171/116490 |
| Access Level: | acceso abierto |
| Palabra clave: | Oncolytic Adenovirus Osteosarcoma Delta-24-ACT |
| id |
ES_c194d82c32e2256bc898f8d61ebbb4dc |
|---|---|
| oai_identifier_str |
oai:dadun.unav.edu:10171/116490 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune memMartinez-Velez, N. (Naiara)|||/items/691b094b-c17c-4084-be40-caea58286559Laspidea, V. (Virginia)|||/items/16d4f649-0742-47dc-a391-881d6cfb978fZalacain-Díez, M. (Marta)|||/items/c9a0a606-4b28-4f43-b423-2bd8ca984432Labiano-Almiñana, S. (Sara)|||/items/65de3442-2f0f-4c20-8e40-43525bb58657Garcia-Moure, M. (Marc)|||/items/9741d07b-2525-4e98-9bfc-93fc3e869273Puigdelloses-Vallcorba, M. (Montserrat)|||/items/658120d0-6a3c-4bf3-9446-33a9234f787eMarrodán-Fernández, L. (Lucía)|||/items/cb588714-8640-4468-a1e4-ea467d9fe714Gonzalez-Huarriz, M. (Marisol)|||/items/00a6d7fb-7851-4264-bdfd-9172d60bc40bHerrador-Cañete, G. (Guillermo)|||/items/91f6f4a9-1383-4ec6-b17f-a914248ff8b0Nava-Martín, D. (Daniel) de la|||/items/9d3a254f-7e46-4632-8066-48e55de9acbdAusejo-Mauleón, I. (Iker)|||/items/5dc64e9f-8695-4947-a007-886bda06f2a5Fueyo, J. (Juan)|||/items/a4e5ff79-2565-4461-ab26-34868ff5ff4dGomez-Manzano, C. (Candelaria)|||/items/5e8d7495-6be8-46e1-8303-cfd722d30166Patiño-García, A. (Ana)|||/items/d68c74f1-df22-4e04-9b77-9cf48fd87b46Alonso-Roldán, M.M. (Marta María)|||/items/b912e21e-f895-4efe-bc4c-de1ca8f36c37Oncolytic AdenovirusOsteosarcomaDelta-24-ACTOsteosarcoma is an aggressive bone tumor occurring primarily in pediatric patients. Despite years of intensive research, the outcomes of patients with metastatic disease or those who do not respond to therapy have remained poor and have not changed in the last 30 years. Oncolytic virotherapy is becoming a reality to treat local and metastatic tumors while maintaining a favorable safety profile. Delta-24-ACT is a replicative oncolytic adenovirus engineered to selectively target cancer cells and to potentiate immune responses through expression of the immune costimulatory ligand 4-1BB. This work aimed to assess the antisarcoma effect of Delta-24-ACT. MTS and replication assays were used to quantify the antitumor effects of Delta-24-ACT in vitro in osteosarcoma human and murine cell lines. Evaluation of the in vivo antitumor effect and immune response to Delta-24-ACT was performed in immunocompetent mice bearing the orthotopic K7M2 cell line. Immunophenotyping of the tumor microenvironment was characterized by immunohistochemistry and flow cytometry. In vitro, Delta-24-ACT killed osteosarcoma cells and triggered the production of danger signals. In vivo, local treatment with Delta-24-ACT led to antitumor effects against both the primary tumor and spontaneous metastases in a murine osteosarcoma model. Viral treatment was safe, with no noted toxicity. Delta-24-ACT significantly increased the median survival time of treated mice. Collectively, our data identify Delta-24-ACT administration as an effective and safe therapeutic strategy for patients with local and metastatic osteosarcoma. These results support clinical translation of this viral immunotherapy approach.American Association for Cancer ResearchDadun. Depósito Académico Digital Universidad de Navarra20222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/116490reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1164902026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem |
| title |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem |
| spellingShingle |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem Martinez-Velez, N. (Naiara)|||/items/691b094b-c17c-4084-be40-caea58286559 Oncolytic Adenovirus Osteosarcoma Delta-24-ACT |
| title_short |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem |
| title_full |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem |
| title_fullStr |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem |
| title_full_unstemmed |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem |
| title_sort |
Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune mem |
| dc.creator.none.fl_str_mv |
Martinez-Velez, N. (Naiara)|||/items/691b094b-c17c-4084-be40-caea58286559 Laspidea, V. (Virginia)|||/items/16d4f649-0742-47dc-a391-881d6cfb978f Zalacain-Díez, M. (Marta)|||/items/c9a0a606-4b28-4f43-b423-2bd8ca984432 Labiano-Almiñana, S. (Sara)|||/items/65de3442-2f0f-4c20-8e40-43525bb58657 Garcia-Moure, M. (Marc)|||/items/9741d07b-2525-4e98-9bfc-93fc3e869273 Puigdelloses-Vallcorba, M. (Montserrat)|||/items/658120d0-6a3c-4bf3-9446-33a9234f787e Marrodán-Fernández, L. (Lucía)|||/items/cb588714-8640-4468-a1e4-ea467d9fe714 Gonzalez-Huarriz, M. (Marisol)|||/items/00a6d7fb-7851-4264-bdfd-9172d60bc40b Herrador-Cañete, G. (Guillermo)|||/items/91f6f4a9-1383-4ec6-b17f-a914248ff8b0 Nava-Martín, D. (Daniel) de la|||/items/9d3a254f-7e46-4632-8066-48e55de9acbd Ausejo-Mauleón, I. (Iker)|||/items/5dc64e9f-8695-4947-a007-886bda06f2a5 Fueyo, J. (Juan)|||/items/a4e5ff79-2565-4461-ab26-34868ff5ff4d Gomez-Manzano, C. (Candelaria)|||/items/5e8d7495-6be8-46e1-8303-cfd722d30166 Patiño-García, A. (Ana)|||/items/d68c74f1-df22-4e04-9b77-9cf48fd87b46 Alonso-Roldán, M.M. (Marta María)|||/items/b912e21e-f895-4efe-bc4c-de1ca8f36c37 |
| author |
Martinez-Velez, N. (Naiara)|||/items/691b094b-c17c-4084-be40-caea58286559 |
| author_facet |
Martinez-Velez, N. (Naiara)|||/items/691b094b-c17c-4084-be40-caea58286559 Laspidea, V. (Virginia)|||/items/16d4f649-0742-47dc-a391-881d6cfb978f Zalacain-Díez, M. (Marta)|||/items/c9a0a606-4b28-4f43-b423-2bd8ca984432 Labiano-Almiñana, S. (Sara)|||/items/65de3442-2f0f-4c20-8e40-43525bb58657 Garcia-Moure, M. (Marc)|||/items/9741d07b-2525-4e98-9bfc-93fc3e869273 Puigdelloses-Vallcorba, M. (Montserrat)|||/items/658120d0-6a3c-4bf3-9446-33a9234f787e Marrodán-Fernández, L. (Lucía)|||/items/cb588714-8640-4468-a1e4-ea467d9fe714 Gonzalez-Huarriz, M. (Marisol)|||/items/00a6d7fb-7851-4264-bdfd-9172d60bc40b Herrador-Cañete, G. (Guillermo)|||/items/91f6f4a9-1383-4ec6-b17f-a914248ff8b0 Nava-Martín, D. (Daniel) de la|||/items/9d3a254f-7e46-4632-8066-48e55de9acbd Ausejo-Mauleón, I. (Iker)|||/items/5dc64e9f-8695-4947-a007-886bda06f2a5 Fueyo, J. (Juan)|||/items/a4e5ff79-2565-4461-ab26-34868ff5ff4d Gomez-Manzano, C. (Candelaria)|||/items/5e8d7495-6be8-46e1-8303-cfd722d30166 Patiño-García, A. (Ana)|||/items/d68c74f1-df22-4e04-9b77-9cf48fd87b46 Alonso-Roldán, M.M. (Marta María)|||/items/b912e21e-f895-4efe-bc4c-de1ca8f36c37 |
| author_role |
author |
| author2 |
Laspidea, V. (Virginia)|||/items/16d4f649-0742-47dc-a391-881d6cfb978f Zalacain-Díez, M. (Marta)|||/items/c9a0a606-4b28-4f43-b423-2bd8ca984432 Labiano-Almiñana, S. (Sara)|||/items/65de3442-2f0f-4c20-8e40-43525bb58657 Garcia-Moure, M. (Marc)|||/items/9741d07b-2525-4e98-9bfc-93fc3e869273 Puigdelloses-Vallcorba, M. (Montserrat)|||/items/658120d0-6a3c-4bf3-9446-33a9234f787e Marrodán-Fernández, L. (Lucía)|||/items/cb588714-8640-4468-a1e4-ea467d9fe714 Gonzalez-Huarriz, M. (Marisol)|||/items/00a6d7fb-7851-4264-bdfd-9172d60bc40b Herrador-Cañete, G. (Guillermo)|||/items/91f6f4a9-1383-4ec6-b17f-a914248ff8b0 Nava-Martín, D. (Daniel) de la|||/items/9d3a254f-7e46-4632-8066-48e55de9acbd Ausejo-Mauleón, I. (Iker)|||/items/5dc64e9f-8695-4947-a007-886bda06f2a5 Fueyo, J. (Juan)|||/items/a4e5ff79-2565-4461-ab26-34868ff5ff4d Gomez-Manzano, C. (Candelaria)|||/items/5e8d7495-6be8-46e1-8303-cfd722d30166 Patiño-García, A. (Ana)|||/items/d68c74f1-df22-4e04-9b77-9cf48fd87b46 Alonso-Roldán, M.M. (Marta María)|||/items/b912e21e-f895-4efe-bc4c-de1ca8f36c37 |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Oncolytic Adenovirus Osteosarcoma Delta-24-ACT |
| topic |
Oncolytic Adenovirus Osteosarcoma Delta-24-ACT |
| description |
Osteosarcoma is an aggressive bone tumor occurring primarily in pediatric patients. Despite years of intensive research, the outcomes of patients with metastatic disease or those who do not respond to therapy have remained poor and have not changed in the last 30 years. Oncolytic virotherapy is becoming a reality to treat local and metastatic tumors while maintaining a favorable safety profile. Delta-24-ACT is a replicative oncolytic adenovirus engineered to selectively target cancer cells and to potentiate immune responses through expression of the immune costimulatory ligand 4-1BB. This work aimed to assess the antisarcoma effect of Delta-24-ACT. MTS and replication assays were used to quantify the antitumor effects of Delta-24-ACT in vitro in osteosarcoma human and murine cell lines. Evaluation of the in vivo antitumor effect and immune response to Delta-24-ACT was performed in immunocompetent mice bearing the orthotopic K7M2 cell line. Immunophenotyping of the tumor microenvironment was characterized by immunohistochemistry and flow cytometry. In vitro, Delta-24-ACT killed osteosarcoma cells and triggered the production of danger signals. In vivo, local treatment with Delta-24-ACT led to antitumor effects against both the primary tumor and spontaneous metastases in a murine osteosarcoma model. Viral treatment was safe, with no noted toxicity. Delta-24-ACT significantly increased the median survival time of treated mice. Collectively, our data identify Delta-24-ACT administration as an effective and safe therapeutic strategy for patients with local and metastatic osteosarcoma. These results support clinical translation of this viral immunotherapy approach. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022-01-01 2022 2022-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/116490 |
| url |
https://hdl.handle.net/10171/116490 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| 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 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
American Association for Cancer Research |
| publisher.none.fl_str_mv |
American Association for Cancer Research |
| dc.source.none.fl_str_mv |
reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
| instname_str |
Universidad de Navarra |
| reponame_str |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
| collection |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869418571640078336 |
| score |
15,811543 |