1. Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells
- Author
-
Alberto Villanueva, Xavier Matias-Guiu, Iñaki Etxeberria, Jara Palomero, J.M. Piulats, Alvaro Teijeira, Ignacio Melero, Miguel F. Sanmamed, Itziar Otano, Arantza Azpilikueta, Jose I. Quetglas, Elixabet Bolaños, Uxua Mancheño, Maria C. Ochoa, Alena Gros, M. Angela Aznar, Sandra Hervas-Stubbs, Saray Garasa, Inmaculada Rodriguez, Pedro Berraondo, August Vidal, Irene Olivera, Sara Labiano, Susana Inogés, and Alfonso R. Sánchez-Paulete
- Subjects
0301 basic medicine ,Cancer Research ,Adoptive cell transfer ,medicine.drug_class ,medicine.medical_treatment ,Melanoma, Experimental ,CD8-Positive T-Lymphocytes ,Monoclonal antibody ,Immunotherapy, Adoptive ,Mice ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Cancer immunotherapy ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Chemistry ,CD137 ,Antibodies, Monoclonal ,Dendritic Cells ,Cell Biology ,T lymphocyte ,Adoptive Transfer ,Interleukin-12 ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Interleukin 12 ,CD8 ,T-Lymphocytes, Cytotoxic - 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.
- Published
- 2019
- Full Text
- View/download PDF