Therapeutic Efficacy and Systemic Antitumor T Cell Immunity Induced by RheoSwitch-Regulated IL-12 Expression after Intratumoral Injection of Adenovirus Vector or Vector-Transduced Dendritic Cells

Interleukin-12 (IL-12) is a potent immunostimulatory cytokine that activates the innate and adaptive cellular immune system and has shown significant therapeutic activity in preclinical models, but severe toxicity of systemically administered IL-12 in cancer patients has limited clinical utilization. Direct delivery into the tumor, along with regulated gene expression, provides a process that may limit the toxic side effects due to high systemic levels of IL-12. Utilizing the RheoSwitch Therapeutic System® (RTS®) expression platform and an orally active activator ligand, intratumoral injections of dendritic cells transduced with adenovirus vector (Ad)-RTS-IL-12 or the Ad-RTS-IL-12 itself into the tumor have induced significant antitumor activity in mouse tumor models and are currently being assessed in clinical trials. The demonstration of RTS-IL-12 proof-of-principle provides a foundation for potential RTS-regulated expression of various therapeutic genes for a variety of cancers or other diseases, using a viral- or cellular-based approach to enhance treatment safety and therapeutic efficacy.