scholarly journals Whole-Body Imaging to Assess Cell-Based Immunotherapy: Preclinical Studies with an Update on Clinical Translation

2021 ◽  
Author(s):  
Noriko Sato ◽  
Peter L. Choyke
Keyword(s):  
T Cell ◽  
Cell Tracking ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Clinical Translation ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Body Imaging ◽  
Cell Therapies

AbstractIn the past decades, immunotherapies against cancers made impressive progress. Immunotherapy includes a broad range of interventions that can be separated into two major groups: cell-based immunotherapies, such as adoptive T cell therapies and stem cell therapies, and immunomodulatory molecular therapies such as checkpoint inhibitors and cytokine therapies. Genetic engineering techniques that transduce T cells with a cancer-antigen-specific T cell receptor or chimeric antigen receptor have expanded to other cell types, and further modulation of the cells to enhance cancer targeting properties has been explored. Because cell-based immunotherapies rely on cells migrating to target organs or tissues, there is a growing interest in imaging technologies that non-invasively monitor transferred cells in vivo. Here, we review whole-body imaging methods to assess cell-based immunotherapy using a variety of examples. Following a review of preclinically used cell tracking technologies, we consider the status of their clinical translation.

scholarly journals T-cell calcium dynamics visualized in a ratiometric tdTomato-GCaMP6f transgenic reporter mouse

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Tobias X Dong ◽  
Shivashankar Othy ◽  
Amit Jairaman ◽  
Jonathan Skupsky ◽  
Angel Zavala ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Tracking ◽  
Cell Types ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Specific Cell ◽  
Transgenic Expression ◽  
Reporter Mouse

Calcium is an essential cellular messenger that regulates numerous functions in living organisms. Here, we describe development and characterization of ‘Salsa6f’, a fusion of GCaMP6f and tdTomato optimized for cell tracking while monitoring cytosolic Ca2+, and a transgenic Ca2+ reporter mouse with Salsa6f targeted to the Rosa26 locus for Cre-dependent expression in specific cell types. The development and function of T cells was unaffected in Cd4-Salsa6f mice. We describe Ca2+ signals reported by Salsa6f during T cell receptor activation in naive T cells, helper Th17 T cells and regulatory T cells, and Ca2+ signals mediated in T cells by an activator of mechanosensitive Piezo1 channels. Transgenic expression of Salsa6f enables ratiometric imaging of Ca2+ signals in complex tissue environments found in vivo. Two-photon imaging of migrating T cells in the steady-state lymph node revealed both cell-wide and localized sub-cellular Ca2+ transients (‘sparkles’) as cells migrate.

scholarly journals Whole-Body Imaging of Sequestration of Plasmodium falciparum in the Rat

2005 ◽  
Vol 73 (11) ◽  
pp. 7736-7746 ◽  
Author(s):  
Fredrik Pettersson ◽  
Anna M. Vogt ◽  
Cathrine Jonsson ◽  
Bobo W. Mok ◽  
Alireza Shamaei-Tousi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Whole Body ◽  
Surgical Removal ◽  
Whole Body Imaging ◽  
Rat Lung ◽  
Body Imaging

ABSTRACT The occlusion of vessels by packed Plasmodium falciparum-infected (iRBC) and uninfected erythrocytes is a characteristic postmortem finding in the microvasculature of patients with severe malaria. Here we have employed immunocompetent Sprague-Dawley rats to establish sequestration in vivo. Human iRBC cultivated in vitro and purified in a single step over a magnet were labeled with 99mtechnetium, injected into the tail vein of the rat, and monitored dynamically for adhesion in the microvasculature using whole-body imaging or imaging of the lungs subsequent to surgical removal. iRBC of different lines and clones sequester avidly in vivo while uninfected erythrocytes did not. Histological examination revealed that a multiadhesive parasite adhered in the larger microvasculature, inducing extensive intravascular changes while CD36- and chondroitin sulfate A-specific parasites predominantly sequester in capillaries, inducing no or minor pathology. Removal of the adhesive ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), preincubation of the iRBC with sera to PfEMP1 or preincubation with soluble PfEMP1-receptors prior to injection significantly reduced the sequestration. The specificity of iRBC binding to the heterologous murine receptors was confirmed in vitro, using primary rat lung endothelial cells and rat lung cryosections. In offering flow dynamics, nonmanipulated endothelial cells, and an intact immune system, we believe this syngeneic animal model to be an important complement to existing in vitro systems for the screening of vaccines and adjunct therapies aiming at the prevention and treatment of severe malaria.

scholarly journals T Cell Calcium Dynamics Visualized in a Ratiometric tdTomato-GCaMP6f Transgenic Reporter Mouse

2017 ◽  
Author(s):  
Tobias X. Dong ◽  
Shivashankar Othy ◽  
Amit Jairaman ◽  
Jonathan Skupsky ◽  
Angel Zavala ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Tracking ◽  
Cell Types ◽  
Cell Receptor ◽  
Functional Expression ◽  
Specific Cell ◽  
Transgenic Expression ◽  
Reporter Mouse

AbstractCalcium is an essential cellular messenger that regulates numerous functions in living organisms. Here we describe development and characterization of “Salsa6f”, a fusion of GCaMP6f and tdTomato optimized for cell tracking while monitoring cytosolic Ca2+, and a transgenic Ca2+ reporter mouse with Salsa6f floxed and targeted to the Rosa26 locus for expression in specific cell types. Using CD4-Cre-Salsa6f mice, we report normal development and function of T cells expressing Salsa6f and demonstrate Ca2+ signaling dynamics during T cell receptor engagement in naïve T cells, helper Th17 T cells and regulatory T cells. Salsa6f expression also revealed functional expression of mechanosensitive Piezo1 channels in T cells. Transgenic expression of Salsa6f enables ratiometric imaging of Ca2+ signals in complex tissue environments found in vivo. Deep tissue two-photon imaging of T cells in the steady-state lymph node revealed a highly localized Ca2+ signaling behavior (“sparkles”) as cells migrate.

scholarly journals In Vivo Magnetic Resonance Tracking of Magnetically Labeled Cells after Transplantation

2002 ◽  
Vol 22 (8) ◽  
pp. 899-907 ◽  
Author(s):  
Jeff W. M. Bulte ◽  
Ian D. Duncan ◽  
Joseph A. Frank
Keyword(s):  
Stem Cell ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Superparamagnetic Iron Oxide ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Body Imaging ◽  
Stem And Progenitor Cells ◽  
The Central Nervous System

During the last few years, the therapeutic use of stem and progenitor cells as a substitute for malfunctioning endogenous cell populations has received considerable attention. Unlike their current use in animal models, the introduction of therapeutic cells in patients will require techniques that can monitor their tissue biodistribution noninvasively. Among the different imaging modalities, magnetic resonance (MR) imaging offers both near-cellular (i.e., 25- to 50-μ) resolution and whole-body imaging capability. In order to be visualized, cells must be labeled with an intracellular tracer molecule that can be detected by MR imaging. Methods have now been developed that make it possible to incorporate sufficient amounts of superparamagnetic iron oxide into cells, enabling their detection in vivo using MR imaging. This is illustrated for (neural stem cell—derived) magnetically labeled oligodendroglial progenitors, transplanted in the central nervous system of dysmyelinated rats. Cells can be followed in vivo for at least 6 weeks after transplantation, with a good histopathologic correlation including the formation of myelin. Now that MR tracking of magnetically labeled cells appears feasible, it is anticipated that this technique may ultimately become an important tool for monitoring the efficacy of clinical (stem) cell transplantation protocols.

scholarly journals Immunotherapy for Glioma: From Illusion to Realistic Prospects?

2014 ◽  
pp. 51-59 ◽  
Author(s):  
Pierre-Yves Dietrich ◽  
Valérie Dutoit ◽  
Paul R. Walker
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Cell Receptor ◽  
High Avidity ◽  
Antigen Receptors ◽  
T Cell Therapy ◽  
Preferential Expression

There is now evidence that the rules established for tumor immunology and immunotherapy in general are relevant for brain tumors. Treatment strategies explored have mainly involved vaccines using either tumor cells or components, and vaccines with defined synthetic peptides. This latter approach offers the advantage to select well-characterized antigens with selective or preferential expression on glioma. This is a prerequisite because collateral damage to the brain is not allowed. A second strategy which is reaching clinical trials is T cell therapy using the patients' own lymphocytes engineered to become tumor reactive. Tumor specificity can be conferred by forced expression of either a high-avidity T cell receptor or an antitumor antibody (the latter cells are called chimeric antigen receptors). An advantage of T cell engineering is the possibility to modify the cells to augment cellular activation, in vivo persistence and resistance to the tumor immunosuppressive milieu. A direct targeting of the hostile glioma microenvironment will additionally be required for achieving potent immunotherapy and various trials are assessing this issue. Finally, combining immunotherapy with immune checkpoint inhibitors and chemotherapy must be explored within rigorous clinical trials that favor constant interactions between the bench and bedside. Regarding immunotherapy for glioma patients, what was an unrealistic dream a decade ago is today a credible prospect.

scholarly journals Advancing Molecular Therapies through In Vivo Bioluminescent Imaging

2003 ◽  
Vol 2 (2) ◽  
pp. 153535002003031
Author(s):  
Anton McCaffrey ◽  
Mark A. Kay ◽  
Christopher H. Contag
Keyword(s):  
Immune Cell ◽  
Expression Patterns ◽  
Whole Body ◽  
Laboratory Animals ◽  
Bioluminescent Imaging ◽  
Light Sources ◽  
Whole Body Imaging ◽  
Cell Therapies ◽  
Imaging Methods

Effective development of therapeutics that target the molecular basis of disease is dependent on testing new therapeutic moieties and delivery strategies in animal models of human disease. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide data in real time and are sensitive to the subtle changes, are crucial for rapid advancement of these approaches. Modalities based on optics are rapid, sensitive, and accessible methods for in vivo analyses with relatively low instrumentation costs. In vivo bioluminescent imaging (BLI) is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity. BLI is based on the use of light-emitting enzymes as internal biological light sources that can be detected externally as biological indicators. BLI has been used to test spatio-temporal expression patterns of both target and therapeutic genes in living laboratory animals where the contextual influences of whole biological systems are preserved. BLI has also been used to analyze gene delivery, immune cell therapies, and the in vivo efficacy of inhibitory RNAs. New tools for BLI are being developed that will offer greater flexibility in detection and analyses. BLI can be used to accelerate the evaluation of experimental therapeutic strategies and whole body imaging offers the opportunity of revealing the effects of novel approaches on key steps in disease processes.

scholarly journals Immuno-oncology: developing integrated approaches toward clinical success of biologics and small-molecule modulators

2020 ◽  
Vol 2 (2) ◽  
pp. FDD23 ◽  
Author(s):  
Shilina Roman ◽  
Sanne Holt ◽  
Julia Schueler
Keyword(s):  
Immune System ◽  
T Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Cell Receptor ◽  
Cell Therapies ◽  
Under Performing ◽  
Small Molecule Modulators

Immuno-oncology (IO) therapy is an exciting emerging pillar of cancer treatment that embraces the concept of modulating the immune system to recognize tumor cells and target them for destruction by either harnessing the effects of the immune system or preventing the evasion of tumor cells from therapeutic targeting. However, our immune system is constantly in a delicate balance between under-performing immune cells failing to manage pathogens, infections or cancer and over-performing immune cells potentially causing autoimmune disorders or cytokine release storms. Over the last 30 years, IO has progressed considerably with approvals for the use of various IO therapeutics including vaccines, cytokines, tumor-directed monoclonal antibodies, immune checkpoint inhibitors as well as chimeric antigen receptor (CAR) and T-cell receptor (TCR) engineered T-cell therapies.

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