Paradoxical Decrease in the Capture and Lymph Node Delivery of Cancer Vaccine Antigen Induced by a TLR4 Agonist as Visualized by Dual-Mode Imaging

Abstract

Traditionally, cell-mediated immune responses to vaccination in animal models are evaluated by invasive techniques such as biopsy and organ extraction. We show here that by combining two non-invasive imaging technologies, magnetic resonance imaging (MRI) and bioluminescence imaging (BLI), we can visualize both the afferent and efferent arms of cellular events following vaccination longitudinally. To this end, we evaluated the immune response elicited by a novel toll-like receptor 4 agonist vaccine adjuvant, glucopyranosyl lipid A (GLA), using a whole cell tumor vaccine. Following magnetovaccination, MRI was used to visualize antigen presenting cell-mediated antigen capture and subsequent migration to draining lymph nodes (DLN). Paradoxically, we observed that the incorporation of GLA in the vaccine reduced these critical parameters of the afferent immune response. For the efferent arm, the magnitude of the ensuing antigen-specific T cell response in DLN visualized using BLI correlated with antigen delivery to the DLN as measured by MRI. These findings were confirmed using flow cytometry. In spite of the GLA associated reduction in antigen delivery to the DLN however, the use of GLA as a vaccine adjuvant led to a massive proliferation of vaccine primed antigen-specific T cells in the spleen. This was accompanied by an enhanced tumor therapeutic effect of the vaccine. These findings suggest that GLA adjuvant changes the temporal and anatomical features of both the afferent and efferent arms of the vaccine response and illustrates the utility of quantitative non-invasive imaging as a tool for evaluating these parameters during vaccine optimization.

89Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies

“…cells has limited sensitivity due to the negative contrast of iron superimposed on a highly heterogeneous background (13)(14)(15). Although techniques that use perfluorocarbon agents to label cells ex vivo and visualize positive signals with fluorine 19 ( 19 F) MR imaging have been rapidly developing, the requirement of a dedicated coil installation and relatively weak signal of 19 F could still be constraints (16)(17)(18)(19).…”

Transplanted adipose-derived stem cells can be short-lived yet accelerate healing of acid-burn skin wounds: a multimodal imaging study

“…Here, we compare a very sensitive but less specific superparamagnetic iron oxide (SPIO) with a very specific but less sensitive fluorine to learn about their usefulness for tracking of stem cells transplanted in a very specific conditions of the skin wound imaging. The concept of magnetic resonance imaging (MRI) of SPIO-labeled cells was introduced over two decades ago 28 and has been especially useful for cell-tracking in the brain 29 and lymph nodes 30 – 32 . However, the cell detection through image hypointensities within superficial areas of tissue injury can be complicated by the presence of susceptibility artifacts at air-tissue interfaces, such as the skin.…”

Quantification and tracking of genetically engineered dendritic cells for studying immunotherapy

“…After demonstrating that pyrrolo‐dC accumulates exclusively in Dm‐dNK–expressing cells, and that this accumulation can be detected both with optical (fluorescence) and MR (CEST) imaging in vitro, we examined the feasibility of monitoring the cells labeled with Dm‐dNK/pyrrolo‐dC in vivo. To that end, we used a well‐established mouse model relevant to immunotherapy— dendritic cell cancer vaccines (Fig. a)—tracking them from the site of injection (the footpad) to the popliteal lymph node.…”

“…MRI-labeling of DCs with iron oxides has been used in the clinic and has demonstrated the importance of the ability to identify precisely the injection site (43). Similarly, several studies have been performed to monitor activated antigen-presenting DCs in draining lymph nodes and to optimize cell-mediated immune responses to antitumor vaccination (39,40). Fluorine ( 19 F) MRI also has been used to label DCs in a mouse model (44) and in humans (45).…”