Nanomedicine for Cancer Immunotherapy: Tracking Cancer-Specific T-Cellsin Vivowith Gold Nanoparticles and CT Imaging

Abstract

Application of immune cell-based therapy in routine clinical practice is challenging due to the poorly understood mechanisms underlying success or failure of treatment. Development of accurate and quantitative imaging techniques for noninvasive cell tracking can provide essential knowledge for elucidating these mechanisms. We designed a novel method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with state-of-the-art nanotechnology. Herein, T-cells were transduced to express a melanoma-specific T-cell receptor and then labeled with gold nanoparticles (GNPs) as a CT contrast agent. The GNP-labeled T-cells were injected intravenously to mice bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T-cells. Using CT, we found that transduced T-cells accumulated at the tumor site, as opposed to nontransduced cells. Labeling with gold nanoparticles did not affect T-cell function, as demonstrated both in vitro, by cytokine release and proliferation assays, and in vivo, as tumor regression was observed. Moreover, to validate the accuracy and reliability of the proposed cell tracking technique, T-cells were labeled both with green fluorescent protein for fluorescence imaging, and with GNPs for CT imaging. A remarkable correlation in signal intensity at the tumor site was observed between the two imaging modalities, at all time points examined, providing evidence for the accuracy of our CT cell tracking abilities. This new method for cell tracking with CT offers a valuable tool for research, and more importantly for clinical applications, to study the fate of immune cells in cancer immunotherapy.

Role of targeting nanoparticles for cancer immunotherapy and imaging

“…In a comparison study of CT imaging to fluorescence imaging, T cells dual-labeled with AuNPs and reporter gene overexpressing green fluorescent protein (GFP) demonstrated si milar trends of T cells distribution and movement in vivo. The incorporated AuNPs also acted as anti-tumor agents in this system, in that targeted T-cells with AuNPs-labeling significantly inhibited tumor progression compared to nontargeted or nontreated controls or AuNPs alone [64] .…”

Gold Nanoparticles as X-Ray, CT, and Multimodal Imaging Contrast Agents: Formulation, Targeting, and Methodology

“…AuNP were incubated with T cells transformed to express a melanoma-specific T-cell receptor before being injected intravenously into mice bearing human melanoma xenografts. The internalized particles were tracked using CT and cells were found to accumulate in the melanomas, while nontransformed cells did not [68].…”

Nanomedicine in Melanoma: Current Trends and Future Perspectives

“…Meir et al have shown in melanoma-bearing mice that labeled GNPs can track tumor-specific T-cells using whole body CT. This approach is a next-generation imaging technique as well as a new tool in immunotherapy (59).…”