Abstract 3575: Cell therapy with surface-tethered IL-12 improves anti-tumor efficacy and activates the endogenous immune system

Adoptive cellular therapy (ACT) has shown impressive clinical responses in some hematologic malignancies. Progress for ACT in solid tumors, however, has been comparatively limited. A key challenge has been overcoming the immunosuppressive microenvironment of solid tumors, which limits T cell activation and persistence. To overcome this barrier, we have further developed our Deep PrimingTM platform to support delivery of therapeutic payloads that activate both the adaptive and innate immune system in the tumor microenvironment. Our Deep PrimingTM technology was designed to function predominantly in an autocrine fashion. To enable transpresentation and paracrine activity we ‘tethered9 cytokines to the T cell surface by constructing a fusion between an immunostimulatory cytokine and an antibody targeting abundant receptors on the T cell surface. This approach is versatile and enables tunable loading and persistence of multiple cytokines on the T cell surface. It also complements transgenic TCR and CAR-T cell therapies without the additional complexities or potential risks associated with further genetic engineering. Interleukin-12 (IL-12) is a potent cytokine with the potential to reshape the anti-inflammatory environment in solid tumors. However, its clinical utility has been limited by severe toxicities both from soluble administration or from adoptively transferred T cells engineered to secrete IL-12. By linking IL-12 to antibodies targeting T cell surface receptors such as CD45 we have improved control of dose and distribution. In in vitro model systems, surface-tethered IL-12 activated signaling on both the loaded T cells and on co-incubated, non-tethered cells (p Citation Format: Jon Nardozzi, Elena Geretti, De-Kuan Chang, Douglas W. McMillin, Jesse Lyons, Ulrik Nielsen, Thomas Andresen, Douglas Jones. Cell therapy with surface-tethered IL-12 improves anti-tumor efficacy and activates the endogenous immune system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3575.