Immunotherapeutic effects of intratumoral nanoplexed poly I:C

Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results i...

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Autores: Aznar, M.A. (María Ángela)|||/items/8a93c205-a638-4589-8774-64166348f62c, Planelles, M. (María)|||/items/dc14a64f-f595-4063-95b1-19e07219f2ba, Perez-Olivares, M. (Mercedes)|||/items/570da771-63e7-4cbd-8804-146f8e273b84, Molina, C. (Carmeen)|||/items/ab58ebab-8343-4857-9c58-b735ac06a44d, Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713, Etxeberria, I. (Iñaki)|||/items/73830f45-c05b-49ed-a21a-f7cbacfc8f07, Perez, G. (Guiomar)|||/items/31ddb848-8e35-4186-908e-2098e84f7ba6, Rodriguez, I. (Inmaculada)|||/items/1de605b4-b2b9-4754-8a45-990e5e3895dd, Bolaños-Mateo, E. (Elixabet)|||/items/073a1977-5579-4bd1-8604-98b3ccfd4361, Lopez-Casas, P. (Pedro)|||/items/c7c23114-a8ff-432e-8e5a-38854494a508, Rodriguez-Ruiz, M.E. (María Esperanza)|||/items/bb89f8c4-6380-4de3-8dd0-877dbf28ef44, Perez-Gracia, J.L. (Jose Luis)|||/items/7be82c5d-4858-4e04-bd77-7ef5a883021b, Marquez-Rodas, I. (Iván)|||/items/a59fa425-b0b0-47e3-9eb6-0543b7132a0c, Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30, Quintero, M. (Marisol)|||/items/610e3591-b74e-40e5-8ccf-55901a1dc22c, Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/57958
Acceso en línea:https://hdl.handle.net/10171/57958
Access Level:acceso abierto
Palabra clave:BO-112
Intratumoral immunotherapy
Nanoplexed poly I:C
Descripción
Sumario:Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment with BO-112 of subcutaneous tumors derived from MC38, 4 T1 and B16- F10 leads to remarkable local disease control dependent on type-1 interferon and gamma-interferon. Some degree of control of non-injected tumor lesions following BO-112 intratumoral treatment was found in mice bearing bilateral B16-OVA melanomas, an activity which was enhanced with co-treatment with systemic anti-CD137 and anti-PD-L1 mAbs. More abundant CD8+ T lymphocytes were found in B16-OVA tumor-draining lymph nodes and in the tumor microenvironment following intratumoral BO-112 treatment, with enhanced numbers of tumor antigen-specific cytotoxic T lymphocytes. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Inspired by these data, intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098).

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