Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/20.500.12008/56429

Título:

Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity

Otros títulos:

Coordinador:

Director:

Compilador:

Autor:

Silva-Pilipich, Noelia
Martisova, Eva
Ballesteros-Briones, María Cristina
Hervas-Stubbs, Sandra
Casares, Noelia
González-Sapienza, Gualberto
Smerdou, Cristian
Vanrell, Lucia

Tutor:

Tipo de documento:

Artículo

Editor:

Palabras clave:

nanobody
VHH
PD-1
PD-L1
AAV vector
cancer
gene therapy
immunotherapy

Descriptores:

Año de publicación:

2020

Contenido:

Resumen:

Immune checkpoint blockade using monoclonal antibodies (mAbs) able to block programmed death-1 (PD-1)/PD-L1 axis represents a promising treatment for cancer. However, it requires repetitive systemic administration of high mAbs doses, often leading to adverse effects. We generated a novel nanobody against PD-1 (Nb11) able to block PD-1/PD-L1 interaction for both mouse and human molecules. Nb11 was cloned into an adeno-associated virus (AAV) vector downstream of four different promoters (CMV, CAG, EF1α, and SFFV) and its expression was analyzed in cells from rodent (BHK) and human origin (Huh-7). Nb11 was expressed at high levels in vitro reaching 2–20 micrograms/mL with all promoters, except SFFV, which showed lower levels. Nb11 in vivo expression was evaluated in C57BL/6 mice after intravenous administration of AAV8 vectors. Nb11 serum levels increased steadily along time, reaching 1–3 microgram/mL two months post-treatment with the vector having the CAG promoter (AAV-CAG-Nb11), without evidence of toxicity. To test the antitumor potential of this vector, mice that received AAV-CAG-Nb11, or saline as control, were challenged with colon adenocarcinoma cells (MC38). AAV-CAG-Nb11 treatment prevented tumor formation in 30% of mice, significantly increasing survival. These data suggest that continuous expression of immunomodulatory nanobodies from long-term expression vectors could have antitumor effects with low toxicity.

Descripción:

metadata.articulos.dc.description.uri:

Editorial:

EN:

Biomedicines. 8, 2020

Financiadores:

Agencia Nacional de Investigación e Innovación (ANII)
Comisión Sectorial de Investigación Científica (CSIC)

Citación:

SILVA-PILIPICH, N., MARTISOVA, E., BALLESTEROS-BRIONES, MC., y otros. Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity. Biomedicines [en línea] 2020, 8. DOI: 10.3390/biomedicines8120562

Citación:

metadata.articulos.cc.license.name:

ISBN:

e-ISBN:

ISSN:

ISMN:

Otros identificadores:

Cobertura geográfica:

Cobertura temporal:

Departamento académico:

Grupo de investigación:

Licencia:

Licencia Creative Commons Atribución (CC - By 4.0)

Colecciones:

Artículos
FicherosDescripciónTamañoFormato
Long-Term Systemic Expression of a Novel.pdf Artículo original 3.09 MB Adobe PDF
Mostrar el registro Dublin Core completo del ítem