2026-04-28T19:44:32Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/818902026-04-15T06:37:24Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

A novel early memory-enriched allogeneic NKG2D CAR-T cell therapy based on CRISPR/Cas9 technology for solid tumors Aparicio Fernández, Cristina Queipo Riera, Mónica Belver, Marina Espeso, Francisco Serna Pérez, Julia Enríquez Rodríguez, Lucía Acebal, Carlos Martín Muñoz, Álvaro Valeri, Antonio Leivas, Alejandra Río, Paula Powell, Daniel J. Lobo Valentín, Rosa María Arrabal, David Martínez López, Joaquín Sánchez, Ana Fuente García, Miguel Ángel de la González-Vallinas Garrachón, Margarita Producción Científica 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 manufacture by 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. 2026-01-20T15:42:57Z 2026-01-20T15:42:57Z 2025 info:eu-repo/semantics/article Cancers, 2025, vol. 17, n. 19, p. 3186. 2072-6694 https://uvadoc.uva.es/handle/10324/81890 10.3390/cancers17193186 3186 19 Cancers 17 2072-6694 eng https://www.mdpi.com/2072-6694/17/19/3186 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Attribution-NonCommercial-NoDerivatives 4.0 Internacional Multidisciplinary Digital Publishing Institute SI