Synopsis
Using magnetoGVAX and MRI for serially monitoring the afferent arm of
the immune response (DCs), and bioluminescent imaging (BLI) for monitoring the efferent
arm (T cells), one can apply dual-mode imaging to better understand the time
course of antigen capture, lymph node delivery, and clonal T cell expansion.
Depending on the timing of administration, immunoadjuvants either
reduce or enhance antigen capture and delivery to the lymph nodes. The lack
of antigen delivery to lymph nodes can be consistent with the lack of T cell BLI
signal in the lymph nodes. In those
cases, a massive extranodal T cell proliferation occurs in the liver and
spleen. These types of studies can show how dual-mode imaging can be used to evaluate and
optimize combinatorial cancer vaccines.
Target Audience
ISMRM students, postdoctoral trainees, faculty, past presidents, members emiritus, or anyone interested to hear about the latest in cancer vaccine imaging.
Outcome/Objectives
To realize that two modes of imaging (BLI and MRI) offer advantages over one mode of imaging, allowing visualization of both the afferent (dendritic cell) and efferent (T cell) arm of the immune system.
Purpose
Further
clinical optimization of the dose, route, vaccine composition, and use of
immunoadjuvants could greatly benefit from clinical imaging approaches that can
interrogate the biological fate of cells repeatedly and non-invasively without
the need for obtaining biopsiesMethods
By pre-la)beling dendritic ells (DCs) with superparamagnetic iron oxide (SPIO) or fluorine (19F) nanoparticles as
an MRI contrast agent, it is not only possible to follow their migration to
nearby lymph nodes, but also to verify if the injections have been performed
accurately. Surprisingly, in a first clinical DC MRI cell tracking study, itb was shown that the target lymph node was routinely misinjected in 50% of stage IV
melanoma patients.
A different kind of cancer
vaccine developed at Johns Hopkins University is GVAX, which consists of lethally
irradiated tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF. By pre-labeling GVAX with
SPIO, we developed “magnetovaccination” as a novel MRI technique to monitor
serially over time DC antigen capture and subsequent homing to draining lymph
nodes. Using magnetoGVAX and MRI for serially monitoring the afferent arm of
the immune response (DCs), and bioluminescent imaging (BLI) for monitoring the efferent
arm (T cells), we applied dual-mode imaging to better understand the time
course of antigen capture, lymph node delivery, and clonal T cell expansion.Results
Depending
on the timing of administration, toll-like-receptor (TLR) agonists either reduced
or enhanced antigen capture and delivery to the lymph nodes. The lack of
antigen delivery to lymph nodes was consistent with the lack of T cell BLI
signal in the lymph nodes. In those
cases, a massive extranodal T cell proliferation occurred in the liver and
spleen.Conclusion
Our studies show how dual-mode imaging can be used to evaluate and
optimize combinatorial cancer vaccines.Acknowledgements
No acknowledgement found.References
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