RT info:eu-repo/semantics/article
T1 A novel early memory-enriched allogeneic NKG2D CAR-T cell therapy based on CRISPR/Cas9 technology for solid tumors
A1 Aparicio, Cristina
A1 Queipo, Mónica
A1 Belver, Marina
A1 Espeso, Francisco
A1 Serna-Pérez, Julia
A1 Enríquez-Rodríguez, Lucía
A1 Acebal, Carlos
A1 Martín-Muñoz, Álvaro
A1 Valeri, Antonio
A1 Leivas, Alejandra
A1 Río, Paula
A1 Powell, Daniel J.
A1 Lobo-Valentín, Rosa
A1 Arrabal, David
A1 Martínez-López, Joaquín
A1 Sánchez, Ana
A1 de la Fuente, Miguel Á.
A1 González-Vallinas, Margarita
K1 Linfocitos T
K1 Alogénico
K1 Off-the-shelf
K1 Tumores sólidos
K1 Memoria inmunológica
K1 CRISPR
K1 NKG2D
K1 Interleuquinas
K1 Inmunoterapia
K1 Cancer
K1 Receptor de antígeno quimérico (CAR)
AB Chimeric Antigen Receptor (CAR)-T cell therapy has shown significant success in treating hematological cancers, but commercialized autologous CAR-T therapies face challenges such as high costs, manufacturing delays, complex standardization and the risk of tumor relapses due to single-antigen targeting. To address these issues, a novel allogeneic CAR-T therapy with broader target specificity was developed, optimizing its manufacturing process. Using CRISPR/Cas9, TCR and HLA class I complex expression were eliminated from donor T cells to reduce the risk of immune rejection and graft-versus-host disease. Additionally, NKG2D CAR, targeting eight ligands upregulated in both solid and hematological tumors, was lentivirally transduced. This study optimized CAR-T cell manufactureby testing various interleukin supplements (IL-2, IL-7/IL-15, IL-7/IL-15/IL-21). Results showed that IL-7/IL-15/IL-21 supplementation produced CAR-T cells with the most suitable characteristics in terms of genetic modification efficiency, cell proliferation, antitumor activity and memory profile. This new allogeneic NKG2D CAR-T therapy represents a promising universal treatment for a variety of cancers.
PB Multidisciplinary Digital Publishing Institute
SN 2072-6694
YR 2025
FD 2025
LK https://uvadoc.uva.es/handle/10324/81890
UL https://uvadoc.uva.es/handle/10324/81890
LA eng
NO Cancers, Septiembre 2025, vol. 17, n. 19, p. 3186.
NO Producción Científica
DS UVaDOC
RD 20-ene-2026