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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.

Original publication




Journal article


Cancer cell

Publication Date





613 - 629.e7


Program of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Avenida de Pio XII, 55, 31008 Pamplona, Spain; Navarra Institute for Health Research (IDISNA), Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.


Dendritic Cells, CD8-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Lymphocytes, Tumor-Infiltrating, Cell Line, Tumor, Animals, Humans, Mice, Melanoma, Experimental, Interleukin-12, Antibodies, Monoclonal, Adoptive Transfer, Immunotherapy, Adoptive