Abstract 4285: Visualizing cancer vaccine clearance in vivo using magnetic resonance imaging

Magnetic Resonance Imaging (MRI) is a powerful tool in the evaluation of immunotherapies, since it permits non-invasive longitudinal assessment of tumor growth, and as our group has previously demonstrated, it allows monitoring of immune response via volumetric changes in lymph nodes (LNs) adjacent to (inguinal LNs) or distant from (popliteal LNs) the site of vaccination. MRI also offers potential for visualizing the uptake behavior of vaccines such as DepoVaxTM, a novel liposome-in-oil-based vaccine platform developed by Immunovaccine Inc. In the context of cancer immunotherapy, this platform uses tumor-associated antigens (TAA), adjuvant and stimulator of T helper cells encapsulated in liposomes and suspended in oil. The oil substrate of the DepoVaxTM immunotherapy vaccine platform acts as an adjuvant that greatly increases the potency of the vaccines, eliciting a strong cytotoxic T-cell response, and also permits longitudinal visualization of the vaccine site with MRI. However, this does not reveal any information about the clearance time of the individual vaccine components, particularly the TAAs. By attaching superparamagnetic iron oxide (SPIO) to the TAA and then encapsulating it in liposomes, it is possible to visualize the biodistribution of the TAA over time using MRI and evaluate whether there is truly a slow clearance of the antigen from the depot site, facilitating a prolonged immune response. In this study, tumor-bearing mice challenged with C3 cells (HPV16 tumor model) were evaluated for the longitudinal clearance of the DepoVaxTM vaccine components using SPIO conjugated to the TAA or associated with the lipid component of the vaccine. The SPIO-conjugated antigen was also tested in a Montanide® oil emulsion vaccine as a control. Over the course of this study, we observed the vaccine being distributed to the surrounding tissue from the injection site, and the antigen was actively transported from the vaccine depot site. The iron-labeled antigen cleared slowly but consistently, decreasing by approximately 40% over 35 days. This study provides direct in vivo evidence that DepoVaxTM resides at the vaccine injection site for a prolonged period of time, increasing exposure to antigen in a controlled fashion, which is likely a key factor in the enhanced immune response elicited by this novel depot vaccine.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 4285. doi:1538-7445.AM2012-4285

Duke Scholars

Author Nikki Pelot