Abstract 2331: Intratumor adoptive transfer of IL-12 mRNA transiently engineered anti-tumor CD8+ T cells

Adoptive T-cell therapy with TILs, CAR-T cells, and TCR-engineered T-cells is achieving remarkable clinical efficacy. Retroviral gene transfer of IL-12 into the T cell cultures markedly enhances efficacy but has shown unacceptable severe side effects in the clinic. To ensure transient gene transfer, tumor specific CD8 T cells were engineered by electroporation of mRNA encoding single chain IL-12 into OT1 and Pmel-1 TCR transgenic lymphocytes. Engineered T cells were injected intratumorally and achieved complete rejections not only of the injected lesion but also of distant concomitant tumors. Efficacy was further enhanced if a small dose of agonist anti-CD137 mAb was co-injected or if CD137-ligand mRNA was co-electroporated. Importantly, intratumor T-cell administration was more efficacious that the intravenous or subcutaneous routes. Therapeutic effects were dependent on IFNγ, cDC1 dendritic cells and endogenous T cells. Interestingly, treatment induced epitope spreading of the immune response to antigens not recognized by the adoptively transferred lymphocytes. Efficacy was also achieved when mouse TILs cultures were used and human TIL cultures can also be transiently IL-12 mRNA engineered. Intratumor release, transient IL-12 mRNA-engineering and repeated administration jointly constitute a safe, feasible and powerful cancer immunotherapy strategy. Note: This abstract was not presented at the meeting. Citation Format: Inaki Etxeberria, Elixabet Bolanos, Alvaro Teijeira, Arantza Azpilicueta, Jose Ignacio Quetglas, Alfonso Rodriguez Sanchez-Paulete, Itziar Otano, Uxua Mancheno, Sandra Hervas-Stubbs, Susana Inoges, Saray Garasa, Maite Alvarez, Pedro Berraondo, Ignacio Melero. Intratumor adoptive transfer of IL-12 mRNA transiently engineered anti-tumor CD8+ T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2331.