1109. Targeting CYP1B1 with a Therapeutic Cancer Vaccine: Results of Preclinical and Clinical Studies

Injection of microparticle encapsulated DNA has been shown to elicit immune responses to the plasmid-encoded antigens, and the use of this technology in a therapeutic cancer vaccine is described. The tumor-associated antigen Cytochrome P450 1B1 (CYP1B1) is overexpressed in many tumor types, but has a relatively restricted normal tissue expression profile, making tumors that express it excellent targets for immunotherapy. Despite the fact that it is a self protein, T cells specific for CYP1B1 epitopes exist in the human repertoire, and these are cytotoxic for tumor cells expressing the antigen. Microparticle formulations containing plasmid DNA are phagocytosed by antigen presenting cells resulting in the expression of the antigen-encoding DNA in cell types well suited for inducing an immune response. Preclinical studies in mice have demonstrated that a formulation made of PLGA microparticles encapsulating a CYP1B1 encoding plasmid DNA are able to induce immune response to CYP1B1. Additionally, it appears that the microparticle formulation has natural adjuvant activity and is amenable to alterations that result in enhanced immunity. This formulation has been tested in a phase I clinical trial of 17 patients with various cancers types, and was shown to be safe and well tolerated. Interestingly, clinical efficacy appeared to correlate with immune responses induced by the drug, leading to strategies to further potentiate the immune response in subsequent trials.