Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells

Publication date: Available online 21 November 2019Source: Cancer CellAuthor(s): Iñaki Etxeberria, Elixabet Bolaños, Jose I. Quetglas, Alena Gros, Alberto Villanueva, Jara Palomero, Alfonso R. Sánchez-Paulete, Jose María Piulats, Xavier Matias-Guiu, Irene Olivera, Maria C. Ochoa, Sara Labiano, Saray Garasa, Inmaculada Rodriguez, August Vidal, Uxua Mancheño, Sandra Hervás-Stubbs, Arantza Azpilikueta, Itziar Otano, M. Angela AznarSummaryRetroviral 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.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research