Detalle Publicación

Intratumor adoptive transfer of IL-12 mRNA transiently engineered antitumor CD8+ T cells

Autores: Etxeberria, I.; Bolaños, E.; Quetglas, J. I.; Gros, A.; Villanueva, A.; Palomero, J.; Sánchez-Paulete, A. R.; Piulats, J. M.; Matías-Guiu, X.; Oliveira, I.; Ochoa, M. C.; Labiano, S.; Garasa, S.; Rodríguez, I.; Vidal, A.; Mancheño, U.; Hervas Stubbs, Sandra; Azpilikueta, A.; Otano, I.; Aznar, M. A.; Fernández de Sanmamed Gutiérrez, Miguel; Inoges Sancho, Susana Inmaculada; Berraondo López, Pedro; Teijeira Sánchez, Álvaro; Melero Bermejo, Ignacio (Autor de correspondencia)
Título de la revista: CANCER CELL
ISSN: 1535-6108
Volumen: 36
Número: 6
Páginas: 613 - 629
Fecha de publicación: 2019
Resumen:
Retroviral gene transfer of interleukin-12 (IL-12) into T cells markedly enhances antitumor efficacy upon adoptive transfer but has clinically shown unacceptable severe side effects. To overcome the toxicity, we engineered tumor-specific CD8+ T cells to transiently express IL-12. Engineered T cells injected intratumorally, but not intravenously, led to complete rejections not only of the injected lesion but also of distant concomitant tumors. Efficacy was further enhanced by co-injection with agonist anti-CD137 mAb or by transient co-expression of CD137 ligand. This treatment induced epitope spreading of the endogenous CD8+ T cell immune response in a manner dependent on cDC1 dendritic cells. Mouse and human tumor-infiltrating T lymphocyte cultures can be transiently IL-12 engineered to attain marked immunotherapeutic effects.
DOI: https://doi.org/10.1016/j.ccell.2019.10.006
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