2026-06-14T03:31:33Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/250772025-12-18T12:57:09Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16962col_20.500.12105_19616
Repisalud
author
Morales-Molina, Alvaro
author
Rodriguez-Milla, Miguel A
author
García-Rodriguez, Patricia
author
Hidalgo, Laura
author
Alemany, Ramon
author
Garcia-Castro, Javier
funder
National Institutes of Health Sciences (Japón)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea. NextGenerationEU
funder
Plan de Recuperación, Transformación y Resiliencia (España)
funder
Plan Estatal de Investigación Científica y Técnica y de Innovación
funder
Comunidad de Madrid (España)
funder
Fundación Oncohematología Infantil
funder
Asociación de Familias de Niños con Cáncer de Castilla-La Mancha
funder
Asociación Pablo Ugarte contra el cáncer infantil
2024-10-09T13:04:15Z
2024-10-09T13:04:15Z
2024-09-19
Mol Ther Oncol . 2024 Aug 23;32(3):200863
10.1016/j.omton.2024.200863
2950-3299
Molecular Therapy Oncology
39290319
https://hdl.handle.net/20.500.12105/25077
Oncolytic viruses often face challenges in achieving optimal antitumor immunity as standalone therapies. The penton base RGD-integrin interactions play a significant role in wild-type adenovirus-induced innate immune responses. To modify these responses, we present ISC301, a novel oncolytic adenovirus engineered by deleting the natural RGD motifs in the penton base while incorporating artificial RGD motifs in the fiber knobs. ISC301 demonstrated comparable infectivity, cytotoxic effects, and signaling profiles across various cell types to its parental ICOVIR-5, which retains the penton base RGD motif. In immunodeficient and immunocompetent mouse models, ISC301 exhibited similar antitumor efficacy to ICOVIR-5. However, ISC301 induced higher intratumoral inflammation through NF-κB activation, leading to increased levels of tumor-infiltrating leukocytes and higher proportion of cytotoxic CD8 T cells. In addition, ISC301 elicits a heightened pro-inflammatory response in peripheral blood. Importantly, when combined with CAR T cell therapy, ISC301 exhibited superior antitumor efficacy, surpassing monotherapy outcomes. These findings emphasize the impact of adenoviral modifications on antitumor immune responses. The deletion of penton base RGD motifs enhances ISC301's pro-inflammatory profile and boosts CAR T cell therapy efficacy. This study enhances understanding of oncolytic virus engineering strategies, positioning ISC301 as a promising candidate for combined immunotherapeutic approaches in cancer treatment.
eng
CAR T
NKG2D
RGD
T cell
Adenovirus
Immunotherapy
Oncolytic virus
Penton base
Virotherapy
Deletion of the RGD motif from the penton base in oncolytic adenoviruses enhances antitumor efficacy of combined CAR T cell therapy
research article
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
URL
https://repisalud.isciii.es/bitstreams/f8617c59-8261-4d9c-85d4-771bae5269dd/download
File
MD5
e8a90c3f3c659ed89986fa36b6f36a11
4563938
application/pdf
DeletionRGD_MotifFromPenton_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/5ea3fa4b-2675-49ab-82bd-8df4c8451637/download
File
MD5
d123247935044bfc8d1db0a65ebe7a6f
169250
application/pdf
Supple1_DeletionRGD_MotifFromPenton_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/9e03a75d-1d7f-4d22-9b11-7c205becde17/download
File
MD5
88dc0b3d0f8a55d2bec9ef5da142f91f
4732188
application/pdf
Supple2_DeletionRGD_MotifFromPenton_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/c4dcc750-e334-4d3f-8bec-56f0b3cf2239/download
File
MD5
d7de0215379c2416931100b0ebf8fa66
71775
text/plain
DeletionRGD_MotifFromPenton_2024.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/d600b461-abbf-4f73-9406-f3a2bd76e075/download
File
MD5
4137602690acc0d172a9d5c39d9e5083
3945
text/plain
Supple1_DeletionRGD_MotifFromPenton_2024.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/76365d33-0220-4f3c-872f-a628e8ef4f40/download
File
MD5
ca4880b8d428de5d37bf571fac1bec27
75719
text/plain
Supple2_DeletionRGD_MotifFromPenton_2024.pdf.txt