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 Fernández, Cristina
A1 Queipo Riera, 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 María
A1 Arrabal, David
A1 Martínez López, Joaquín
A1 Sánchez, Ana
A1 Fuente García, Miguel Ángel de la
A1 González-Vallinas Garrachón, 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 05-mar-2026