This ligand-gated delivery system distinguishes itself by offering precise spatial and temporal control of IL-12 production, directly addressing the dose-limiting toxicities of systemic cytokine therapy. Unlike constitutive gene transfer or bolus injections of recombinant IL-12, local activation within the tumor microenvironment confines immune stimulation to target sites, optimizing CD8+ T cell cross-priming and antitumor efficacy. The ability to toggle cytokine release through simple adjustments in ligand administration routes and concentrations provides unprecedented pharmacodynamic fine-tuning, enabling real-time management of therapeutic windows and minimizing systemic side effects.
Description
This invention provides the field of therapeutics. Most specifically present invention provides methods of generating in vitro engineered dendritic cells conditionally expressing interleukin-12 (IL-12) under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals including human.
Applications
Intratumoral immunotherapy
Controlled IL-12 delivery
Personalized cancer vaccines
Dendritic cell therapy manufacturing
Combination immunotherapy regimens
Advantages
Precise control of IL-12 expression via ligand dosing to minimize systemic toxicity
Enhanced local antitumor immunity through improved CD8+ T cell cross-priming
Ability to turn IL-12 production on or off by adjusting ligand dose, timing, and route
Versatile ligand administration routes (intraperitoneal, oral gavage, in food) for clinical flexibility
Real-time monitoring of efficacy through tumor regression and IFN-γ release assays
Reduced systemic side effects compared to conventional systemic IL-12 therapy
Potential for combination with other therapeutic genes or immune cell types for synergistic effects
IP Status
https://patents.google.com/patent/US9675642B2
