In vivo monitoring of natural killer cell trafficking during tumor immunotherapy

Abstract

Natural killer (NK) cells are a crucial part of the innate immune system and play critical roles in host anti-viral, anti-microbial, and antitumor responses. The elucidation of NK cell biology and their therapeutic use are actively being pursued with 200 clinical trials currently underway. In this review, we outline the role of NK cells in cancer immunotherapies and summarize current noninvasive imaging technologies used to track NK cells in vivo to investigate mechanisms of action, develop new therapies, and evaluate efficacy of adoptive transfer.

Keywords: MRI; PET imaging; cell tracking; immunotherapy; natural killer cells; optical imaging.

Figure 1

Adapted from Tavri et al, with permission. Optical (fluorescence) imaging scans of rats with EpCAM-positive DU145 prostate cancer xenografts (arrow) before and after injection of targeted (NK-92-scFv(MOC31)-zeta) (subject #4) and nontargeted NK-92 cells (subject #7) labeled with DiD. Scans show increases in tumor fluorescence signal at 1.5–24 hours post injection (p.i.) of NK cells. The subject that received nontargeted NK-92 cells shows nonspecific signal in the liver/lung region 1.5–24 hours p.i. The subject that received the targeted NK-92 cells showed the nonspecific liver/lung fluorescence only at 8 hours p.i.

Figure 2

Reprinted with permission from Meier et al. (Left) Representative digital autoradiographs of tumors and organ tissues from mice with HER2/neu-positive sarcoma that received ¹⁸FDG-labeled targeted NK-92 (NK-92-scFv(FRP5)-zeta) cells (A) and nontargeted parental NK-92 cells (B). The signal intensity bar shows count density of photostimulated luminescence per unit area: PSL/mm² (in log scale). (Right) Uptake of radioactivity in selected organs subtracted from the background noise (rectangular box on autoradiograph image).

Figure 3

Reproduced with permission from Meier et al. Axial and coronal T₂*-weighted gradient echo images (TR/TE = 5.1/500 ms) of representative EpCAM-positive DU154 tumors (arrows) before and after injection of ferumoxide-labled targeted NK-92 (NK-92-scFv(MOC31)-zeta) and nontargeted parental NK-92 cells. There is a signal decrease at the tumor site at 1 hour and 24 hours post injection only after administration of ferumoxide-labeled NK-92-scFv(MOC31)-zeta cells.

Figure 4

Axial T₂*-weighted gradient echo images (TR/TE = 1500 ms/3.74 ms) and corresponding R₂* maps (units in s⁻¹) from an NSG mouse implanted with Daudi Burkitt’s lymphoma (arrows) before (pre) and 6 hours post ferumoxytol-labeled NK cell injection (personal communication).