The use of magnetovaccination and magnetic resonance imaging for investigating cancer vaccine dynamics

A major parameter limiting immune responses to vaccination is the number of activated antigen presenting cells (APCs) that capture antigen and migrate to draining lymph nodes (LNs). Currently, a quantitative non-invasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo pre-labeling of cells with contrast agents followed by reintroduction of cells into the animal being monitored. Here we describe an in vivo labeling method which relies upon cell-to-cell transfer of superparamagnetic iron oxides (SPIO) from tumor cells to endogenous antigen presenting cells, in situ, in order to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell-based vaccine that was irradiated and labeled with SPIO. APCs which had captured SPIO were imaged over time as they accumulated in LNs. We show that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by adjuvants. In vivo DC quantification was further utilized to serve as a non-invasive surrogate marker for cancer vaccine efficacy. Antigen specific T cell responses were shown to correlate strongly with the number of DCs found in each draining lymph node. Together these studies demonstrate the potential of magnetovaccination and MRI cell tracking to systematically evaluate key parameters relevant to the optimization of vaccine therapies.