Proof of principle for the feasibility of our proprietary tumor vaccination strategy involving the use of Interleukin-12-encapsulated microspheres has been demonstrated in Phase I studies. A single intra-tumoral injection of Interleukin-12-encapsulated biodegradable microspheres induces the complete regression of small primary tumors, promotes the development of long-term systemic anti-tumor immunity and results in the eradication of established disseminated disease in murine tumor models. In this Phase II application, we propose to perform extensive product development work, complete the toxicology/pharmacology studies and develop a clinical treatment protocol in preparation for IND filing. To this end, in Aims 1, 2 and 3, we will focus on product development studies including analytical assay development (Aim 1), process development for scale-up and stability analysis (Aim 2) and formulation development work to improve product stability (Aim 3). Pharmacokinetic and toxicological characterization of the product will be performed in Aim 4.
In Aim 5, the optimized formulation will be used to evaluate the effect of dose, treatment schedule and booster vaccinations on long-term cure of disseminated disease in a pre-clinical routine tumor model. The optimal treatment strategy identified in Aim 5 will provide the blueprint for a Phase I clinical trial protocol. These studies are expected to generate the data that is necessary for IND approval.
