Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells
2019; Cell Press; Volume: 36; Issue: 6 Linguagem: Inglês
10.1016/j.ccell.2019.10.006
ISSN1878-3686
AutoresIñaki Etxeberría, Elixabet Bolaños, José I. Quetglas, Alena Gros, Alberto Villanueva, Jara Palomero, Alfonso R. Sánchez-Paulete, Josep M. Piulats, Xavier Matías‐Guiu, Irene Olivera, María C. Ochoa, Sara Labiano, Saray Garasa, Inmaculada Rodríguez, August Vidal, Uxua Mancheño, Sandra Hervás‐Stubbs, Arantza Azpilikueta, Itziar Otano, M. Ángela Aznar, Miguel F. Sanmamed, Susana Inogès, Pedro Berraondo, Álvaro Teijeira, Ignacio Melero,
Tópico(s)RNA Interference and Gene Delivery
ResumoSummary 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.
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