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Magnetovaccination as a Novel Method to Assess and Quantify Dendritic Cell Tumor Antigen Capture and Delivery to Lymph Nodes

¹ Department of Biomedical Engineering, ² Department of Oncology, ³ Russel H. Morgan Department of Radiology, Division of MR Research, ⁴ Department of Chemical and Biomolecular Engineering, ⁵ Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland and ⁶ Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands

Requests for reprints: Hyam I. Levitsky, Suite 4M51 CRB I, 1650 Orleans Street, Baltimore, MD 21231. Phone: 410-614-0552; Fax: 410-614-9705; E-mail: hy{at}jhmi.edu or Jeff W.M. Bulte, 720 Rutland Avenue, 217 Traylor Building, Baltimore, MD 21205. E-mail: jwmbulte{at}mri.jhu.edu.

Key Words: dendritic cells • MRI • vaccine

A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, 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 that had captured SPIO were imaged over time as they accumulated in LNs. We show here 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 an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers. [Cancer Res 2009;69(7):3180–7]

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