Labeling of cell therapies: How can we get it right?

Waiczies, Sonia; Niendorf, Thoralf; Lombardi, Giovanna

doi:10.1080/2162402x.2017.1345403

Cited by 12 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In controls cells, the same PFC volume was added, without the incubation step, after the viability measurement and washed three times with PBS. 19 F NMR spectra of control cell pellets did not show residual PFC emulsion, confirming that non-internalized PFC does not pellet during the wash steps 46 .…”

Section: Methodsmentioning

confidence: 65%

Fluorine-19 nuclear magnetic resonance of chimeric antigen receptor T cell biodistribution in murine cancer model

Chapelin

Gao

Okada

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Discovery of effective cell therapies against cancer can be accelerated by the adaptation of tools to rapidly quantitate cell biodistribution and survival after delivery. Here, we describe the use of nuclear magnetic resonance (NMR) ‘cytometry’ to quantify the biodistribution of immunotherapeutic T cells in intact tissue samples. In this study, chimeric antigen receptor (CAR) T cells expressing EGFRvIII targeting transgene were labeled with a perfluorocarbon (PFC) emulsion ex vivo and infused into immunocompromised mice bearing subcutaneous human U87 glioblastomas expressing EGFRvIII and luciferase. Intact organs were harvested at day 2, 7 and 14 for whole-sample fluorine-19 (19F) NMR to quantitatively measure the presence of PFC-labeled CAR T cells, followed by histological validation. NMR measurements showed greater CAR T cell homing and persistence in the tumors and spleen compared to untransduced T cells. Tumor growth was monitored with bioluminescence imaging, showing that CAR T cell treatment resulted in significant tumor regression compared to untransduced T cells. Overall, 19F NMR cytometry is a rapid and quantitative method to evaluate cell biodistribution, tumor homing, and fate in preclinical studies.

show abstract

Section: Methodsmentioning

confidence: 65%

Fluorine-19 nuclear magnetic resonance of chimeric antigen receptor T cell biodistribution in murine cancer model

Chapelin

Gao

Okada

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…MNPs remain on the cell surface in close contact with cell membrane. T cells have typically low phagocytic capacity [41] with large nuclei and reduced cytoplasm, which could impair MNP entry inside the cytoplasm. Moreover, it has been also described that transfection of such cell types has always presented many difficulties and limitations, being a really inefficient process [42–46].…”

Section: Discussionmentioning

confidence: 99%

T cells loaded with magnetic nanoparticles are retained in peripheral lymph nodes by the application of a magnetic field

Sanz-Ortega¹,

Rojas²,

Marcos³

et al. 2019

J Nanobiotechnol

View full text Add to dashboard Cite

BackgroundT lymphocytes are highly dynamic elements of the immune system with a tightly regulated migration. T cell-based transfer therapies are promising therapeutic approaches which in vivo efficacy is often limited by the small proportion of administered cells that reaches the region of interest. Manipulating T cell localisation to improve specific targeting will increase the effectiveness of these therapies. Nanotechnology has been successfully used for localized release of drugs and biomolecules. In particular, magnetic nanoparticles (MNPs) loaded with biomolecules can be specifically targeted to a location by an external magnetic field (EMF). The present work studies whether MNP-loaded T cells could be targeted and retained in vitro and in vivo at a site of interest with an EMF.ResultsT cells were unable to internalize the different MNPs used in this study, which remained in close association with the cell membrane. T cells loaded with an appropriate MNP concentration were attracted to an EMF and retained in an in vitro capillary flow-system. MNP-loaded T cells were also magnetically retained in the lymph nodes after adoptive transfer in in vivo models. This enhanced in vivo retention was in part due to the EMF application and to a reduced circulating cell speed within the organ. This combined use of MNPs and EMFs did not alter T cell viability or function.ConclusionsThese studies reveal a promising approach to favour cell retention that could be implemented to improve cell-based therapy. Electronic supplementary materialThe online version of this article (10.1186/s12951-019-0440-z) contains supplementary material, which is available to authorized users.

show abstract

“…As can be seen in Figure 2b, LY fluorescence of nanoparticle treated cells only increased significantly compared to the control cells after 48 h of incubation. This suggests that internalization of SPION Citrate in primary human T cells can occur after prolonged incubation, but at earlier time points, we suspect that SPION Citrate mainly adhere to the cell surface, particularly as T cells per se are described to typically have low phagocytic activity [37]. This is in line with findings by others who performed transmission electron microscopy analysis of T cells or NK cells incubated with SPIONs for two hours, showing that particles independently of their coating mainly adhered to the plasma membrane [23,25].…”

Section: Cellular Content Of Spion Citratementioning

confidence: 97%

Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation

Mühlberger

Unterweger

Band

et al. 2020

Cells

View full text Add to dashboard Cite

For the conversion of immunologically cold tumors, characterized by a low T cell infiltration, into hot tumors, it is necessary to enrich T cells in the tumor area. One possibility is the use of magnetic fields to direct T cells into the tumor. For this purpose, primary T cells that were freshly isolated from human whole blood were loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONCitrate). Cell toxicity and particle uptake were investigated by flow cytometry and atomic emission spectroscopy. The optimum loading of the T cells without any major effect on their viability was achieved with a particle concentration of 75 µg Fe/mL and a loading period of 24 h. The cellular content of SPIONCitrate was sufficient to attract these T cells with a magnet which was monitored by live-cell imaging. The functionality of the T cells was only slightly influenced by SPIONCitrate, as demonstrated by in vitro stimulation assays. The proliferation rate as well as the expression of co-stimulatory and inhibitory surface molecules (programmed cell death 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain containing 3 (Tim-3), C-C motif chemokine receptor 7 (CCR7), CD25, CD45RO, CD69) was investigated and found to be unchanged. Our results presented here demonstrate the feasibility of loading primary human T lymphocytes with superparamagnetic iron oxide nanoparticles without influencing their viability and functionality while achieving sufficient magnetizability for magnetically controlled targeting. Thus, the results provide a strong fundament for the transfer to tumor models and ultimately for new immunotherapeutic approaches for cancer treatment.

show abstract

Labeling of cell therapies: How can we get it right?

Cited by 12 publications

References 14 publications

Fluorine-19 nuclear magnetic resonance of chimeric antigen receptor T cell biodistribution in murine cancer model

Fluorine-19 nuclear magnetic resonance of chimeric antigen receptor T cell biodistribution in murine cancer model

T cells loaded with magnetic nanoparticles are retained in peripheral lymph nodes by the application of a magnetic field

Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation

Contact Info

Product

Resources

About