scholarly journals Detection and Monitoring of Regulatory Immune Cells Following Their Adoptive Transfer in Organ Transplantation

2020 ◽  
Vol 11 ◽  
Author(s):  
Lillian M. Tran ◽  
Angus W. Thomson
Keyword(s):  
Clinical Trials ◽  
Organ Transplantation ◽  
Immune Cells ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Tolerance Induction ◽  
Current Status ◽  
Transplant Tolerance ◽  
Cell Based Therapy

Application of cell-based immunotherapy in organ transplantation to minimize the burden of immunosuppressive medication and promote allograft tolerance has expanded significantly over the past decade. Adoptively transferred regulatory immune cells prolong allograft survival and transplant tolerance in pre-clinical models. Many cell products are currently under investigation in early phase human clinical trials designed to assess feasibility and safety. Despite rapid advances in manufacturing practices, defining the appropriate protocol that will optimize in vivo conditions for tolerance induction remains a major challenge and depends heavily on understanding the fate, biodistribution, functional stability and longevity of the cell product after administration. This review focuses on in vivo detection and monitoring of various regulatory immune cell types administered for allograft tolerance induction in both pre-clinical animal models and early human clinical trials. We discuss the current status of various non-invasive methods for tracking regulatory cell products in the context of organ transplantation and implications for enhanced understanding of the therapeutic potential of cell-based therapy in the broad context of control of immune-mediated inflammatory disorders.

scholarly journals Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion

Blood ◽  
2009 ◽  
Vol 114 (16) ◽  
pp. 3431-3438 ◽  
Author(s):  
Roch Houot ◽  
Matthew J. Goldstein ◽  
Holbrook E. Kohrt ◽  
June H. Myklebust ◽  
Ash A. Alizadeh ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cells ◽  
Antitumor Immunity ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Adaptive Immune Response ◽  
Primary Lymphoma ◽  
Treg Depletion

Abstract Despite the success of passive immunotherapy with monoclonal antibodies (mAbs), many lymphoma patients eventually relapse. Induction of an adaptive immune response may elicit active and long-lasting antitumor immunity, thereby preventing or delaying recurrence. Immunomodulating mAbs directed against immune cell targets can be used to enhance the immune response to achieve efficient antitumor immunity. Anti-CD137 agonistic mAb has demonstrated antitumor efficacy in various tumor models and has now entered clinical trials for the treatment of solid tumors. Here, we investigate the therapeutic potential of anti-CD137 mAb in lymphoma. We found that human primary lymphoma tumors are infiltrated with CD137+ T cells. We therefore hypothesized that lymphoma would be susceptible to treatment with anti-CD137 agonistic mAb. Using a mouse model, we demonstrate that anti-CD137 therapy has potent antilymphoma activity in vivo. The antitumor effect of anti-CD137 therapy was mediated by both natural killer (NK) and CD8 T cells and induced long-lasting immunity. Moreover, the antitumor activity of anti-CD137 mAb could be further enhanced by depletion of regulatory T cell (Tregs). These results support the evaluation of anti-CD137 therapy in clinical trials for patients with lymphoma.

scholarly journals Advances in Molecular Imaging Strategies forIn VivoTracking of Immune Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ho Won Lee ◽  
Prakash Gangadaran ◽  
Senthilkumar Kalimuthu ◽  
Byeong-Cheol Ahn
Keyword(s):  
Computerized Tomography ◽  
Immune Cells ◽  
Cell Tracking ◽  
Immune Cell ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Nuclear Imaging ◽  
Cell Based Therapy

Tracking of immune cellsin vivois a crucial tool for development and optimization of cell-based therapy. Techniques for tracking immune cells have been applied widely for understanding the intrinsic behavior of immune cells and include non-radiation-based techniques such as optical imaging and magnetic resonance imaging (MRI), radiation-based techniques such as computerized tomography (CT), and nuclear imaging including single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Each modality has its own strengths and limitations. To overcome the limitations of each modality, multimodal imaging techniques involving two or more imaging modalities are actively applied. Multimodal techniques allow integration of the strengths of individual modalities. In this review, we discuss the strengths and limitations of currently available preclinicalin vivoimmune cell tracking techniques and summarize the value of immune cell tracking in the development and optimization of immune cell therapy for various diseases.

scholarly journals Short lifespan of syngeneic transplanted MSC is a consequence of in vivo apoptosis and immune cell recruitment in mice

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Mihai Bogdan Preda ◽  
Carmen Alexandra Neculachi ◽  
Ioana Madalina Fenyo ◽  
Ana-Maria Vacaru ◽  
Mihai Alin Publik ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tracking System ◽  
Luciferase Expression ◽  
Therapeutic Effects ◽  
Post Transplantation ◽  
Cell Based Therapy ◽  
And Migration ◽  
Migration Capacity

AbstractMesenchymal stromal cells (MSC) are attractive tools for cell-based therapy, yet the mechanisms underlying their migration and survival post-transplantation are unclear. Accumulating evidence indicates that MSC apoptosis modulates both innate and adaptive immune responses which impact on MSC therapeutic effects. Using a dual tracking system, namely the Luciferase expression and VivoTrack680 labelling, and in vivo optical imaging, we investigated the survival and migration of MSC transplanted by various routes (intravenous, subcutaneous, intrapancreatic and intrasplenic) in order to identify the best delivery approach that provides an accumulation of therapeutic cells to the injured pancreas in the non-obese diabetic (NOD) mouse. The results showed that transplanted MSC had limited migration capacity, irrespective of the administration route, and were short-lived with almost total disappearance at 7 days after transplantation. Within one day after transplantation, cells activated hypoxia signalling pathways, followed by Caspase 3-mediated apoptosis. These were subsequently followed by local recruitment of immune cells at the transplantation site, and the engulfment of apoptotic MSC by macrophages. Our results argue for a “hit and die” mechanism of transplanted MSC. Further investigations will elucidate the molecular crosstalk between the inoculated and the host-immune cells.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

scholarly journals Toll-Like Receptor-Based Strategies for Cancer Immunotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Saghar Pahlavanneshan ◽  
Ali Sayadmanesh ◽  
Hamidreza Ebrahimiyan ◽  
Mohsen Basiri
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetically Engineered ◽  
Current Status ◽  
Tlr Signaling ◽  
Functional Roles ◽  
Immunotherapy Of Cancer ◽  
Signaling Components

Toll-like receptors (TLRs) are expressed and play multiple functional roles in a variety of immune cell types involved in tumor immunity. There are plenty of data on the pharmacological targeting of TLR signaling using agonist molecules that boost the antitumor immune response. A recent body of research has also demonstrated promising strategies for improving the cell-based immunotherapy methods by inducing TLR signaling. These strategies include systemic administration of TLR antagonist along with immune cell transfer and also genetic engineering of the immune cells using TLR signaling components to improve the function of genetically engineered immune cells such as chimeric antigen receptor-modified T cells. Here, we explore the current status of the cancer immunotherapy approaches based on manipulation of TLR signaling to provide a perspective of the underlying rationales and potential clinical applications. Altogether, reviewed publications suggest that TLRs make a potential target for the immunotherapy of cancer.

scholarly journals Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021

2021 ◽  
Vol 12 ◽  
Author(s):  
Safaet Alam ◽  
Taslima Binte Kamal ◽  
Md. Moklesur Rahman Sarker ◽  
Jin-Rong Zhou ◽  
S. M. Abdur Rahman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Series ◽  
Basic Knowledge ◽  
World Health ◽  
Current Status ◽  
Drug Candidates ◽  
Health Organization ◽  
Meta Analyses

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

scholarly journals Drosophila immune cells extravasate from vessels to wounds using Tre1 GPCR and Rho signaling

2018 ◽  
Vol 217 (9) ◽  
pp. 3045-3056 ◽  
Author(s):  
Leila Thuma ◽  
Deborah Carter ◽  
Helen Weavers ◽  
Paul Martin
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Murine Models ◽  
Pupal Development ◽  
Epithelial Migration ◽  
Drosophila Model ◽  
Rate Limiting ◽  
Insight Into

Inflammation is pivotal to fight infection, clear debris, and orchestrate repair of injured tissues. Although Drosophila melanogaster have proven invaluable for studying extravascular recruitment of innate immune cells (hemocytes) to wounds, they have been somewhat neglected as viable models to investigate a key rate-limiting component of inflammation—that of immune cell extravasation across vessel walls—due to their open circulation. We have now identified a period during pupal development when wing hearts pulse hemolymph, including circulating hemocytes, through developing wing veins. Wounding near these vessels triggers local immune cell extravasation, enabling live imaging and correlative light-electron microscopy of these events in vivo. We show that RNAi knockdown of immune cell integrin blocks diapedesis, just as in vertebrates, and we uncover a novel role for Rho-like signaling through the GPCR Tre1, a gene previously implicated in the trans-epithelial migration of germ cells. We believe this new Drosophila model complements current murine models and provides new mechanistic insight into immune cell extravasation.

scholarly journals Critical Analysis of Non-Thermal Plasma-Driven Modulation of Immune Cells from Clinical Perspective

2020 ◽  
Vol 21 (17) ◽  
pp. 6226 ◽  
Author(s):  
Barbora Smolková ◽  
Adam Frtús ◽  
Mariia Uzhytchak ◽  
Mariia Lunova ◽  
Šárka Kubinová ◽  
...  
Keyword(s):  
Immune Cells ◽  
Thermal Plasma ◽  
Critical Analysis ◽  
Cell Function ◽  
Immune Cell ◽  
Real Life ◽  
Research Strategy ◽  
Cellular Mechanisms ◽  
Non Thermal Plasma

The emerged field of non-thermal plasma (NTP) shows great potential in the alteration of cell redox status, which can be utilized as a promising therapeutic implication. In recent years, the NTP field considerably progresses in the modulation of immune cell function leading to promising in vivo results. In fact, understanding the underlying cellular mechanisms triggered by NTP remains incomplete. In order to boost the field closer to real-life clinical applications, there is a need for a critical overview of the current state-of-the-art. In this review, we conduct a critical analysis of the NTP-triggered modulation of immune cells. Importantly, we analyze pitfalls in the field and identify persisting challenges. We show that the identification of misconceptions opens a door to the development of a research strategy to overcome these limitations. Finally, we propose the idea that solving problems highlighted in this review will accelerate the clinical translation of NTP-based treatments.

scholarly journals Effect of Low-Immunogenic Yogurt Drinks and Probiotic Bacteria on Immunoreactivity of Cow’s Milk Proteins and Tolerance Induction—In Vitro and In Vivo Studies

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3390
Author(s):  
Barbara Wróblewska ◽  
Anna Kaliszewska-Suchodoła ◽  
Ewa Fuc ◽  
Lidia Hanna Markiewicz ◽  
Anna Maria Ogrodowczyk ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Tolerance Induction ◽  
Milk Proteins ◽  
In Vivo Studies ◽  
Cow’S Milk ◽  
Milk Allergy ◽  
Cow's Milk ◽  
Safe Product

There is no effective therapy for milk allergy. The role of lactic acid bacteria (LAB) and probiotics in protection against allergy-related outcomes is still under investigation. The aim of the study was to evaluate the immunomodulative and therapeutic potential of yogurt drinks in cow’s milk allergy (CMA) management. We compared immunoreactivity of α-casein (α-CN), β-casein (β-CN), κ-casein (κ-CN), α-lactalbumin (α-LA), and β-lactoglobulin (β-LG) in 27 yogurt drinks fermented with different basic yogurt cultures, or yogurt cultures enriched with Lactobacillus plantarum and/or Bifidobacterium lactis strains, by competitive ELISA assay. Drinks with the lowest antigenic potential were used as allergoids for CMA therapy. BALB/c mice were sensitized via intraperitoneal injection of α-CN + β-LG mixture with aluminum adjuvant, and gavaged with increasing doses of selected low-immunogenic drinks (YM—basic, or YM-LB—enriched with L. plantarum and B. lactis) to induce tolerance. Milk- or phosphate-buffered saline (PBS)-dosed mice served as controls. Compared to milk, the immunoreactivity of proteins in drinks increased or decreased, depending on the bacterial sets applied for fermentation. Only a few sets acted synergistically in reducing immunoreactivity. The selected low-immunogenic drinks stimulated allergic mice for profiling Th2 to Th1 response and acquire tolerance, and the effect was greater with YM-LB drink, which during long-lasting interventional feeding strongly increased the secretion of regulatory cytokines, i.e., IL-10 and TGF-β, and IgA and decreased IL-4, IgE, and anti-(α-CN + β-LG) IgG1. The studies revealed variations in the potency of yogurt bacteria to change allergenicity of milk proteins and the need for their strict selection to obtain a safe product for allergy sufferers. The YM-LB drink with reduced antigenic potential may be a source of allergoids used in the immunotherapy of IgE mediated CMA, but further clinical or volunteer studies are required.

scholarly journals The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens

2020 ◽  
Vol 21 (9) ◽  
pp. 3347
Author(s):  
Jose-Ignacio Rodriguez-Barbosa ◽  
Pascal Schneider ◽  
Luis Graca ◽  
Leo Bühler ◽  
Jose-Antonio Perez-Simon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Allogeneic Bone Marrow Transplantation ◽  
Tumor Necrosis Factor Receptor ◽  
Tolerance Induction ◽  
Homeostatic Proliferation ◽  
Allogeneic Bone ◽  
Transplant Tolerance ◽  
Conditioning Regimens

Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR.

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