Monocyte Subtype Determination by Labeling with Feraheme Nanoparticles
Mentor: Georges El Fakhri, Ph.D. (Massachusetts General Hospital)
Monocytes are premature macrophages that can become a defense mechanism for cancer cells against the native immune system when they infiltrate into tumors as tumor associated macrophages (TAMs). Monocytes are being studied in the context of immunotherapy, which is an up and coming field in cancer treatment. Immunotherapy aims to use of a patient’s own immune system to target cancer cells. Feraheme (FH) is an FDA-approved nanoparticle (NP) drug which has been shown to be selectively phagocytosed by monocytes and macrophages, allowing for detection and imaging of this cell population. However, it is currently unclear whether all subtypes of monocytes are taking up these nanoparticles in the same way. Part of my project will be investigating if the various subtypes of monocytes phagocytose the NPs in the same manner, or if adjustments need to be done to the makeup of the nanoparticles to ensure that all subtypes of monocytes can be labeled with them. These studies will be performed ex vivo using monocytes purified from whole blood of various animal species, including non-human primates. These cells will be tested using a fluorescently labeled FH-NP, and cross-stained with antibody markers to determine cellular subtypes by flow cytometry. My project will also include PET imaging of tumor-bearing mice injected with a radio-labeled version of the FH-NP, allowing for long-term tracking of the monocyte macrophage distribution in vivo. The long term impact of this research is that it can be used to research the effectiveness of potential cancer treatment drugs while they are being created, as well as effectiveness of the drugs after they are administered using the labeled monocyte tracking.
Monocyte internalization of Cy5.5-FH by dual-wavelength flow cytometry (Box 1 and Box 2). (a) Schematic showing i.v.-injected Cy5.5-FH NPs (red spheres) are internalized by blood-residing monocytes (gray spheres) or phagocytized by hepatic Kupffer cells (purple) in the liver. (b) Four quadrants of dual-wavelength flow cytometry are (1) unlabeled cells, (2) Cy5.5-FH cells, (3) Cy5.5 and anti-CD11b cells (FITC), and (4) anti-CD11b cells (FITC). Source: