KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis
Oncolytic adenoviral therapy is a promising approach for pancreatic cancer treatment. However, the limited capacity of murine cells to produce infectious viral progeny precludes the full evaluation of the virotherapy in a suitable immunocompetent mouse model. Here, we report that the murine KPC-I ce...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Molecular Therapy: Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S295032992400170X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841545490807652352 |
|---|---|
| author | Marc Otero-Mateo Francesc Estrany Jr Sabrina Arcas-Márquez Laura Moya-Borrego Giancarlo Castellano Miquel Castany Ramon Alemany Cristina Fillat |
| author_facet | Marc Otero-Mateo Francesc Estrany Jr Sabrina Arcas-Márquez Laura Moya-Borrego Giancarlo Castellano Miquel Castany Ramon Alemany Cristina Fillat |
| author_sort | Marc Otero-Mateo |
| collection | DOAJ |
| description | Oncolytic adenoviral therapy is a promising approach for pancreatic cancer treatment. However, the limited capacity of murine cells to produce infectious viral progeny precludes the full evaluation of the virotherapy in a suitable immunocompetent mouse model. Here, we report that the murine KPC-I cell line, established from pancreatic tumors developed in LSL-KrasG12D; LSL-Trp53R172H; Pdx-Cre mice, is susceptible to adenoviral replication and generates a progeny of infective virions similar to those from infected human A549 cells. A comparative study with the semipermissive murine CMT64.6 cells reveals that adenoviral infection of KPC-I cells substantially increases the release of infective particles, with a correlating enhanced susceptibility to adenovirus-induced autophagy. Remarkably, systemic delivery of the oncolytic adenovirus AdNuPARE1A in athymic mice bearing KPC-I tumors results in significant inhibition of tumor growth. Moreover, KPC-I tumors in immunocompetent mice with intratumoral administration of AdNuPARE1A or ICOVIR15kDelE3 display significant antitumoral effects, with evidence of adenoviral replication. Collectively, our data show that KPC-I cells are permissive to human oncolytic adenovirus replication, rendering KPC-I syngeneic tumors an interesting model to evaluate the multifaceted antitumor activities of oncolytic adenovirus. |
| format | Article |
| id | doaj-art-296a5554d21c46c18ca2bdcdea5c32ad |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-296a5554d21c46c18ca2bdcdea5c32ad2025-01-12T05:26:24ZengElsevierMolecular Therapy: Oncology2950-32992025-03-01331200928KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysisMarc Otero-Mateo0Francesc Estrany Jr1Sabrina Arcas-Márquez2Laura Moya-Borrego3Giancarlo Castellano4Miquel Castany5Ramon Alemany6Cristina Fillat7Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; Programa de Biomedicina. Universitat de Barcelona, 08036 Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainCancer Immunotherapy Group, Oncobell and iProCURE Programs, IDIBELL-Institut Català d’Oncologia, 08908 L’Hospitalet de Llobregat, Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainCancer Immunotherapy Group, Oncobell and iProCURE Programs, IDIBELL-Institut Català d’Oncologia, 08908 L’Hospitalet de Llobregat, Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 08036 Barcelona, Spain; Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona, 08036 Barcelona, Spain; Corresponding author: Cristina Fillat, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainOncolytic adenoviral therapy is a promising approach for pancreatic cancer treatment. However, the limited capacity of murine cells to produce infectious viral progeny precludes the full evaluation of the virotherapy in a suitable immunocompetent mouse model. Here, we report that the murine KPC-I cell line, established from pancreatic tumors developed in LSL-KrasG12D; LSL-Trp53R172H; Pdx-Cre mice, is susceptible to adenoviral replication and generates a progeny of infective virions similar to those from infected human A549 cells. A comparative study with the semipermissive murine CMT64.6 cells reveals that adenoviral infection of KPC-I cells substantially increases the release of infective particles, with a correlating enhanced susceptibility to adenovirus-induced autophagy. Remarkably, systemic delivery of the oncolytic adenovirus AdNuPARE1A in athymic mice bearing KPC-I tumors results in significant inhibition of tumor growth. Moreover, KPC-I tumors in immunocompetent mice with intratumoral administration of AdNuPARE1A or ICOVIR15kDelE3 display significant antitumoral effects, with evidence of adenoviral replication. Collectively, our data show that KPC-I cells are permissive to human oncolytic adenovirus replication, rendering KPC-I syngeneic tumors an interesting model to evaluate the multifaceted antitumor activities of oncolytic adenovirus.http://www.sciencedirect.com/science/article/pii/S295032992400170Xoncolytic adenovirusimmunocompetent modelspancreatic tumorsKPC cellsautophagyadenovirus replication |
| spellingShingle | Marc Otero-Mateo Francesc Estrany Jr Sabrina Arcas-Márquez Laura Moya-Borrego Giancarlo Castellano Miquel Castany Ramon Alemany Cristina Fillat KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis Molecular Therapy: Oncology oncolytic adenovirus immunocompetent models pancreatic tumors KPC cells autophagy adenovirus replication |
| title | KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis |
| title_full | KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis |
| title_fullStr | KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis |
| title_full_unstemmed | KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis |
| title_short | KPC pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis |
| title_sort | kpc pancreatic cancer cells are a novel immunocompetent murine model supporting human adenovirus replication and tumor oncolysis |
| topic | oncolytic adenovirus immunocompetent models pancreatic tumors KPC cells autophagy adenovirus replication |
| url | http://www.sciencedirect.com/science/article/pii/S295032992400170X |
| work_keys_str_mv | AT marcoteromateo kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis AT francescestranyjr kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis AT sabrinaarcasmarquez kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis AT lauramoyaborrego kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis AT giancarlocastellano kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis AT miquelcastany kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis AT ramonalemany kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis AT cristinafillat kpcpancreaticcancercellsareanovelimmunocompetentmurinemodelsupportinghumanadenovirusreplicationandtumoroncolysis |