Abstract 1964: Development of a nanovaccine for cancer therapy

Abstract

Purpose: Despite significant advancements in dendritic cell (DC)-based cancer immunotherapy, the approach remains challenging, especially with regard to developing a simple yet robust method for activating the immune system against cancer in the context of using tumor antigen-activated DCs. To improve the feasibility of this immunotherapy approach, we sought to develop a robust vaccine that utilizes nanotechnology to activate endogenous DCs in the host. Method: Using a superparamagnetic iron oxide (SPIO) nanoparticle as the carrier for this therapy, two immune system activating molecules were conjugated to the nanoparticle. The dextran-coated SPIO nanoparticles were reacted with an epoxyamine linker to produce amine groups on the surface of the nanoparticle. Next, a potent Natural Killer T (NKT) cell activating glycolipid, was conjugated to the SPIO nanoparticle via a disulfide-containing crosslinker. For in vivo studies, an MUC-1 derived antigenic peptide was conjugated as well to the same nanoparticles. Here, adult MUC-1 transgenic C57BL/6 mice were implanted with MUC-1 transfected C57G tumors. The protein and adjuvant conjugated nanoparticle was delivered to mice via subcutaneous injection. Tumor growth in the treated and untreated groups of mice was measured by ultrasound over a 5-week period. Results: Using a mouse model, the effectiveness of a nanovaccine was determined. The nanoparticle conjugated with the NKT cell agonist induced robust IFN-γ and IL-4 response in wild-type mice while no response was elicited in NKT cell- or DC-deficient mice probed with the same nanovaccine. In a different mouse model group, treatment of tumor-bearing MUC-1 animals with the nanovaccine resulted in markedly diminished tumor growth compared to the untreated group. Conclusion: The results indicate that the nanoparticle delivery vehicle can induce a robust immune response in mice. Beyond this vehicular capability, the SPIO nanoparticles can be used as contrast agents for magnetic resonance imaging. As a result, this multimodal and multivalent nanovaccine, achieved through nanotechnology, has the potential to provide microanatomical and functional imaging feedback of the DC-targeted anti-cancer immunotherapy, thus leading to longitudinal treatment and monitoring. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1964. doi:1538-7445.AM2012-1964