title: Nanomedicine for Cancer Immunotherapy: Tracking Cancer-Specific T-Cells in Vivo with 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.
authors.affiliation: †Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Rinat
authors.initials: R
authors.lastname: Meir
authors.affiliation: ‡Laboratory of Tumor Immunology and Immunotherapy, Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Katerina
authors.initials: K
authors.lastname: Shamalov
authors.affiliation: †Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Oshra
authors.initials: O
authors.lastname: Betzer
authors.affiliation: †Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Motiei
authors.affiliation: ‡Laboratory of Tumor Immunology and Immunotherapy, Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Miryam
authors.initials: M
authors.lastname: Horovitz-Fried
authors.affiliation: §The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Yehuda
authors.affiliation: ∥Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa 49100, Israel.
authors.forename: Aron
authors.initials: A
authors.lastname: Popovtzer
authors.affiliation: †Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Rachela
authors.initials: R
authors.lastname: Popovtzer
authors.affiliation: ‡Laboratory of Tumor Immunology and Immunotherapy, Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Cyrille J
authors.initials: CJ
authors.lastname: Cohen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058948:Cell Tracking; D005260:Female; D006046:Gold / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D007167:Immunotherapy; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D050997:Nanomedicine; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014057:Tomography, X-Ray Computed
chemical_list: D006046:Gold
keywords: T cells; cancer; cell therapy; cell tracking; computed tomography; imaging; immunotherapy