scholarly journals Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules

2021 ◽  
Vol 22 (16) ◽  
pp. 9051
Author(s):  
Cole W. D. Peters ◽  
Fares Nigim
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Small Molecule ◽  
Viral Vectors ◽  
Adaptive Immune System ◽  
The Body ◽  
General Effect ◽  
Viral Lysis ◽  
Tumor Killing ◽  
A Cell

The dogma of engineering oncolytic viral vectors has shifted from emphasizing the viral lysis of individual cancer cells to the recruitment and coordination of the adaptive immune system to clear the tumor. To accomplish this, researchers have been adding several classes of transgenes to their preferred viral platforms. The most prevalent of these include antibodies and targeting moieties, interleukins and cytokines, and genes which rely on small molecule co-administration for tumor killing. Most current vectors rely exclusively on one of these types of transgenes to elicit the desired immune response to clear tumors, but are not mutually exclusive, with several larger OVs armed with several of these factors. The common theme of emerging armed vectors is to simply initiate or enhance infiltration of effector CD8+ T cells to clear the tumor locally at OV infection sites, and systemically throughout the body where the OV has not infected tumor cells. The precision of oncolytic vectors to target a cell type or tissue remains its key advantage over small-molecule drugs. Unlike chemo- and other drug therapies, viral vectors can be made to specifically infect and grow within tumor cells. This ensures localized expression of the therapeutic transgene to the diseased tissue, thereby limiting systemic toxicity. This review will examine the immunomodulating transgenes of current OVs, describe their general effect on the immune system, and provide the rationale for each vector’s use in clearing its targeted tumor.

scholarly journals Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Shiho Chiba ◽  
Hiroaki Ikushima ◽  
Hiroshi Ueki ◽  
Hideyuki Yanai ◽  
Yoshitaka Kimura ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Tumoricidal Activity ◽  
Effector Cells ◽  
Therapeutic Implications ◽  
Tumor Killing

The eradication of tumor cells requires communication to and signaling by cells of the immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. Here, we show that the innate immune receptor Dectin-1 expressed on dendritic cells and macrophages is critical to NK-mediated killing of tumor cells that express N-glycan structures at high levels. Receptor recognition of these tumor cells causes the activation of the IRF5 transcription factor and downstream gene induction for the full-blown tumoricidal activity of NK cells. Consistent with this, we show exacerbated in vivo tumor growth in mice genetically deficient in either Dectin-1 or IRF5. The critical contribution of Dectin-1 in the recognition of and signaling by tumor cells may offer new insight into the anti-tumor immune system with therapeutic implications.

scholarly journals Discovery of Novel Small Molecule Inhibitors of VEGF Expression in Tumor Cells Using a Cell-Based High Throughput Screening Platform

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0168366 ◽  
Author(s):  
Liangxian Cao ◽  
Marla Weetall ◽  
Jenelle Bombard ◽  
Hongyan Qi ◽  
Tamil Arasu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Inhibitors ◽  
Vegf Expression ◽  
A Cell ◽  
Screening Platform

scholarly journals Maximal frustration as an immunological principle

2008 ◽  
Vol 6 (32) ◽  
pp. 321-334 ◽  
Author(s):  
F. Vistulo de Abreu ◽  
P Mostardinha
Keyword(s):  
Immune System ◽  
Fundamental Problem ◽  
Artificial Immune Systems ◽  
Adaptive Immune System ◽  
Cross Reactivity ◽  
Cellular Systems ◽  
The Body ◽  
Apparent Paradox ◽  
Adaptive Immune ◽  
Mathematical Analyses

A fundamental problem in immunology is that of understanding how the immune system selects promptly which cells to kill without harming the body. This problem poses an apparent paradox. Strong reactivity against pathogens seems incompatible with perfect tolerance towards self. We propose a different view on cellular reactivity to overcome this paradox: effector functions should be seen as the outcome of cellular decisions which can be in conflict with other cells' decisions. We argue that if cellular systems are frustrated, then extensive cross-reactivity among the elements in the system can decrease the reactivity of the system as a whole and induce perfect tolerance. Using numerical and mathematical analyses, we discuss two simple models that perform optimal pathogenic detection with no autoimmunity if cells are maximally frustrated. This study strongly suggests that a principle of maximal frustration could be used to build artificial immune systems. It would be interesting to test this principle in the real adaptive immune system.

scholarly journals The Vicious Cross-Talk between Tumor Cells with an EMT Phenotype and Cells of the Immune System

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 460 ◽  
Author(s):  
Elisabetta Romeo ◽  
Carmelo Antonio Caserta ◽  
Cristiano Rumio ◽  
Fabrizio Marcucci
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Large Body ◽  
Adaptive Immune System ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Immune Exclusion

Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). A large body of evidence has shown that EMT tumor cells and immune cells can reciprocally influence each other, with EMT cells promoting immune exclusion and deviation and immune cells promoting, under certain circumstances, the induction of EMT in tumor cells. This cross-talk between EMT tumor cells and immune cells can occur both between EMT tumor cells and cells of either the native or adaptive immune system. In this article, we review this evidence and the functional consequences of it. We also discuss some recent evidence showing that tumor cells and cells of the immune system respond to similar stimuli, activate the expression of partially overlapping gene sets, and acquire, at least in part, identical functionalities such as migration and invasion. The possible significance of these symmetrical changes in the cross-talk between EMT tumor cells and immune cells is addressed. Eventually, we also discuss possible therapeutic opportunities that may derive from disrupting this cross-talk.

scholarly journals C3 AND C4 COMPLEMENT – BIOMARKERS FOR PROGNOSIS OF TREATMENT OF TNF-BLOKERS

2019 ◽  
Vol 32 (2) ◽  
pp. 247-250
Author(s):  
Stanislava Popova ◽  
Mariela Geneva
Keyword(s):  
Immune System ◽  
Complement System ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Response Prediction ◽  
The Body ◽  
Control Group ◽  
Phagocytic Cells ◽  
Immune System Activation ◽  
The Complement System

Introduction: The complement system adds antibodies and helps phagocytic cells to destroy pathogens from the body. This is part of a congenital immune system that is not adaptive and does not change over the individual life. However, complement can be "triggered" by the adaptive immune system. The complement system is the main effector of the humoral patr of the immune system. Activation of complement results in opsonization, chemotaxis and cytolysis. Regulation of the complement system can control inflammatory diseases including psoriatic arthritis and vice versa, complement fixation disorders can lead to illness. Treatment with anti-TNF blokers complement activity in patients with inflammatory joint diseases.Objective: To investigate C3, C4 fractions of complement, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement the response prediction and monitoring of anti-TNF treatment in patients with psoriatic arthritis.Materials and Methods: 36 patients were included sequentially before treatment with TNF-a-blokers. C3, C4, ESR, CRP were assessed at baseline at 6 and 12 months after initiation of treatment with TNF-α blockers. The activity of the disease is measured by the DARSA disease activity scale, the responses being compared with a control group of persons similar in gender and age. Statistical data processing was performed using the SPSS v25.Results and conclusions: According to the results obtained, C3 and C4 were significantly higher than controls at initiation of treatment (C3 111.3 ± 30.8, C4 91.9 ± 12.4 mg / dl, controls 19.1 ± 8.3 mg / dl, 10.2 ± 5.6 mg / dl p = 0.001, p = 0.001). At 6 and 12 months of follow-up, 76.2% of patients had a reduction in the level of C3 and C4 (p = 0.002, 0.001, respectively). It was found that higher baseline levels of C3 were associated with higher DARSA values at 6 and 12 months.Conclusion: The study of the C3 and C4 complement fractions can be used as biomarkers to estimate the prognosis of TNF-blocker therapy.

scholarly journals Cooperation and cheating as innovation: insights from cellular societies

2017 ◽  
Vol 372 (1735) ◽  
pp. 20160421 ◽  
Author(s):  
Athena Aktipis ◽  
Carlo C. Maley
Keyword(s):  
Immune System ◽  
Microbial Communities ◽  
Social Systems ◽  
Human Microbiome ◽  
Adaptive Immune System ◽  
The Body ◽  
Adaptive Immune ◽  
Constant Tension ◽  
Cellular Cooperation ◽  
Multicellular Organisms

The capacity to innovate is often considered a defining feature of human societies, but it is not a capacity that is unique to human societies: innovation occurs in cellular societies as well. Cellular societies such as multicellular bodies and microbial communities, including the human microbiome, are capable of innovation in response to novel opportunities and threats. Multicellularity represents a suite of innovations for cellular cooperation, but multicellularity also opened up novel opportunities for cells to cheat, exploiting the infrastructure and resources of the body. Multicellular bodies evolve less quickly than the cells within them, leaving them vulnerable to cellular innovations that can lead to cancer and infections. In order to counter these threats, multicellular bodies deploy additional innovations including the adaptive immune system and the development of partnerships with preferred microbial partners. What can we learn from examining these innovations in cooperation and cheating in cellular societies? First, innovation in social systems involves a constant tension between novel mechanisms that enable greater size and complexity of cooperative entities and novel ways of cheating. Second, cultivating cooperation with partners who can rapidly and effectively innovate (such as microbes) is important for large entities including multicellular bodies. And third, multicellularity enabled cells to manage risk socially, allowing organisms to survive in challenging environments where life would otherwise be impossible. Throughout, we ask how insights from cellular societies might be translated into new innovations in human health and medicine, promoting and protecting the cellular cooperation that makes us viable multicellular organisms. This article is part of the themed issue ‘Process and pattern in innovations from cells to societies’.

scholarly journals Extracorporeal Immunotherapy in Oncology

2019 ◽  
Vol 4 (2) ◽  
Keyword(s):  
Immune System ◽  
Cytotoxic Activity ◽  
Tumor Cells ◽  
Recognition System ◽  
Immune Defense ◽  
The Body ◽  
System State ◽  
Killer Activity ◽  
Apheresis Therapy

Tumors development is closely related to the immune system state and in immunosuppression tumors occur many times more often. The quality of the immune defense depends on how the recognition system functions for malignized tumor cells and its timely destruction. However, the immunosuppression state may be a result of the tumor process itself. The tumor itself generates soluble molecules that inhibit the killer activity of lymphocytes and macrophages, which allows tumor cells to survive in the body. Therefore, it is justified to perform apheresis therapy aimed at removal of such inhibitors, and targeted restoration of cytotoxic activity of leukocytes, which should contribute to the tumor cells apoptosis. This method of extracorporeal immunopharmacotherapy is indicated not only in far-advanced cases, but also after any radical operations, when metastases are not detected and even chemotherapy is not carried out.

scholarly journals Basic concepts in clinical immunology: A review

2021 ◽  
Vol 12 (3) ◽  
pp. 490-496
Author(s):  
Andrew Nakibinge Kiboneka
Keyword(s):  
Immune System ◽  
Blood Cells ◽  
White Blood Cells ◽  
Adaptive Immune System ◽  
The Body ◽  
Molecular Structures ◽  
Natural Immunity ◽  
Hematopoietic Stem ◽  
Effector Cells ◽  
Infection Pattern

Immunity is the state of protection against foreign pathogens or substances(antigens). Host defence mechanisms consist of innate immunity (natural immunity), which mediates the initial protection against infections, and adaptive immunity (specific/acquired immunity), which develops more slowly and provides more specialized and more effective defence against infections. The immune system evolved to protect multicellular organisms against pathogens. The body is protected against pathogens by a variety of effector cells and molecules that together make up the immune system. All the cellular elements of blood, including the red blood cells, platelets and white blood cells of the immune system, ultimately derive from the hematopoietic stem cells of the bone marrow. The cells of the adaptive immune system consist of lymphocytes, antigen-presenting cells and effector cells that eliminate microbes. Strategies of avoidance, and tolerance represent different ways of dealing with pathogens. Anatomic barriers and chemical barriers e.g complement and antimicrobial proteins may be considered as primary forms of avoidance.Macrophages,neutrophils and dendritic cells are important cells that that detect infection. Pattern recognition receptors (PRRs) recognize simple molecules and regular patterns of molecular structures called pathogen associated molecular patterns. Some PRR are transmembrane proteins e.g Toll like receptors (TLRs). Vaccination is a simple, safe, and effective way of protecting people against harmful diseases, before they come into contact with them. Immunization is the process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine. Inappropriate immune responses can result into hypersensitivity, autoimmune disease or immune deficiency.

scholarly journals Inducing Tumor Suppressive Microenvironments through Genome Edited CD47−/− Syngeneic Cell Vaccination

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Subhadra Jayaraman Rukmini ◽  
Huanjing Bi ◽  
Puloma Sen ◽  
Benjamin Everhart ◽  
Sha Jin ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Growth Rates ◽  
The Body ◽  
Immunomodulatory Effects ◽  
Tumor Microenvironments

AbstractTumors can escape from the immune system by overexpressing CD47 and other checkpoint blockades. CD47 is expressed ubiquitously by all cells in the body, posing an obstacle for CD47 blocking treatments due to their systemic toxicity. We performed a study to determine how the tumor microenvironment changes after vaccination with genome edited CD47−/− syngeneic tumor cells. We discovered that inactivated CD47-depleted mouse melanoma cells can protect mice from melanoma. Our animal study indicated that 33% of vaccinated mice remained tumor-free, and 100% of mice had 5-fold reduced growth rates. The characterization of immunomodulatory effects of the vaccine revealed a highly anti-tumorigenic and homogenous microenvironment after vaccination. We observed consistently that in the tumors that failed to respond to vaccines, there were reduced natural killer cells, elevated regulatory T cells, M2-type macrophages, and high PD-L1 expression in these cells. These observations suggested that the tumor microenvironments became more suppressive to tumor growth after vaccination, suggesting a potential new immunotherapy for solid tumors.

scholarly journals Mechanisms of Immunotoxicity: Stressors and Evaluators

2021 ◽  
Vol 22 (15) ◽  
pp. 8242
Author(s):  
Maroun Bou Zerdan ◽  
Sara Moussa ◽  
Ali Atoui ◽  
Hazem I. Assi
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
The Body ◽  
Genetic Defects ◽  
Physical Chemical ◽  
Psychological Stressors ◽  
Immune Deficiencies ◽  
Biochemical Mechanisms

The immune system defends the body against certain tumor cells and against foreign agents such as fungi, parasites, bacteria, and viruses. One of its main roles is to distinguish endogenous components from non-self-components. An unproperly functioning immune system is prone to primary immune deficiencies caused by either primary immune deficiencies such as genetic defects or secondary immune deficiencies such as physical, chemical, and in some instances, psychological stressors. In the manuscript, we will provide a brief overview of the immune system and immunotoxicology. We will also describe the biochemical mechanisms of immunotoxicants and how to evaluate immunotoxicity.

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