| Literature DB >> 31761658 |
Iñaki Etxeberria1, Elixabet Bolaños2, Jose I Quetglas3, Alena Gros4, Alberto Villanueva5, Jara Palomero4, Alfonso R Sánchez-Paulete3, Jose María Piulats6, Xavier Matias-Guiu7, Irene Olivera1, Maria C Ochoa1, Sara Labiano3, Saray Garasa3, Inmaculada Rodriguez1, August Vidal8, Uxua Mancheño3, Sandra Hervás-Stubbs3, Arantza Azpilikueta1, Itziar Otano3, M Angela Aznar3, Miguel F Sanmamed9, Susana Inogés10, Pedro Berraondo1, Álvaro Teijeira1, Ignacio Melero11.
Abstract
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.Entities:
Keywords: CD137; IL-12; TILs; adoptive T cell therapy; cancer immunotherapy; epitope spreading; intratumor delivery; mRNA T cell engineering; monoclonal antibody
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Year: 2019 PMID： 31761658 DOI： 10.1016/j.ccell.2019.10.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743