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Human Vaccines & Immunotherapeutics Oct 2020Oncolytic viruses have been taking the front stage in biological therapy for cancer recently. The first and most potent virus to be used in oncolytic virotherapy is... (Review)
Review
Oncolytic viruses have been taking the front stage in biological therapy for cancer recently. The first and most potent virus to be used in oncolytic virotherapy is human adenovirus. Recently, ongoing extensive research has suggested that other viruses like herpes simplex virus (HSV) and measles virus can also be considered as potential candidates in cancer therapy. An HSV-based oncolytic virus, T-VEC, has completed phase Ш clinical trial and has been approved by the U.S. Food and Drug Administration (FDA) for use in biological cancer therapy. Moreover, the vaccine strain of the measles virus has shown impressive results in pre-clinical and clinical trials. Considering their therapeutic efficacy, safety, and reduced side effects, the use of such engineered viruses in biological cancer therapy has the potential to establish a milestone in cancer research. In this review, we summarize the recent clinical advances in the use of oncolytic viruses in biological therapy for cancer. Additionally, this review evaluates the potential viral candidates for their benefits and shortcomings and sheds light on the future prospects.
Topics: Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32078405
DOI: 10.1080/21645515.2020.1723363 -
Immunity Jun 2017Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform... (Review)
Review
Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma. In this review, we summarize recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful. We will also discuss new methods for purifying and investigating reactive-astrocyte functions and provide an overview of new markers for delineating these different states of reactive astrocytes. The discovery that astrocytes have different types of reactive states has important implications for the development of new therapies for CNS injury and diseases.
Topics: Animals; Astrocytes; Biological Therapy; Brain; Central Nervous System; Humans; Neurodegenerative Diseases; Neurons
PubMed: 28636962
DOI: 10.1016/j.immuni.2017.06.006 -
Trends in Biotechnology Jul 2013Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) comprise a powerful class of tools that are redefining the boundaries of... (Review)
Review
Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) comprise a powerful class of tools that are redefining the boundaries of biological research. These chimeric nucleases are composed of programmable, sequence-specific DNA-binding modules linked to a nonspecific DNA cleavage domain. ZFNs and TALENs enable a broad range of genetic modifications by inducing DNA double-strand breaks that stimulate error-prone nonhomologous end joining or homology-directed repair at specific genomic locations. Here, we review achievements made possible by site-specific nuclease technologies and discuss applications of these reagents for genetic analysis and manipulation. In addition, we highlight the therapeutic potential of ZFNs and TALENs and discuss future prospects for the field, including the emergence of clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases.
Topics: Biological Therapy; Clustered Regularly Interspaced Short Palindromic Repeats; Deoxyribonucleases; Genetic Engineering; Molecular Biology; Recombinant Proteins; Zinc Fingers
PubMed: 23664777
DOI: 10.1016/j.tibtech.2013.04.004 -
Molecular Cancer Sep 2020The activation of the cGAS-STING pathway has tremendous potential to improve anti-tumor immunity by generating type I interferons. In recent decades, we have witnessed... (Review)
Review
The activation of the cGAS-STING pathway has tremendous potential to improve anti-tumor immunity by generating type I interferons. In recent decades, we have witnessed that producing dsDNA upon various stimuli is an initiative factor, triggering the cGAS-SING pathway for a defensive host. The understanding of both intracellular cascade reaction and the changes of molecular components gains insight into type I IFNs and adaptive immunity. Based on the immunological study, the STING-cGAS pathway is coupled to cancer biotherapy. The most challenging problem is the limited therapeutic effect. Therefore, people view 5, 6-dimethylxanthenone-4-acetic acid, cyclic dinucleotides and various derivative as cGAS-STING pathway agonists. Even so, these agonists have flaws in decreasing biotherapeutic efficacy. Subsequently, we exploited agonist delivery systems (nanocarriers, microparticles and hydrogels). The article will discuss the activation of the cGAS-STING pathway and underlying mechanisms, with an introduction of cGAS-STING agonists, related clinical trials and agonist delivery systems.
Topics: Biological Therapy; Carcinogenesis; Humans; Immunotherapy; Interferon Type I; Membrane Proteins; Neoplasms; Nucleotidyltransferases; Signal Transduction; Xanthines
PubMed: 32887628
DOI: 10.1186/s12943-020-01247-w -
Gut Apr 2021Extraintestinal manifestations (EIMs) are frequently observed in IBDs and contribute considerably to morbidity and mortality. They have long been considered a difficult... (Review)
Review
Extraintestinal manifestations (EIMs) are frequently observed in IBDs and contribute considerably to morbidity and mortality. They have long been considered a difficult to treat entity due to limited therapy options, but the increasing use of anti-tumour necrosis factors has dramatically changed the therapeutic approach to EIM in recent years. Newly emerging therapies such as JAK inhibitors and anti-interleukin 12/23 will further shape the available armamentarium. Clinicians dealing with EIMs in everyday IBD practice may be puzzled by the numerous available biological agents and small molecules, their efficacy for EIMs and their potential off-label indications. Current guidelines on EIMs in IBD do not include treatment algorithms to help practitioners in the treatment decision-making process. Herein, we summarise knowledge on emerging biological treatment options and small molecules for EIMs, highlight current research gaps, provide therapeutic algorithms for EIM management and shed light on future strategies in the context of IBD-related EIMs.
Topics: Antibodies, Monoclonal; Biological Therapy; Humans; Inflammatory Bowel Diseases; Tumor Necrosis Factor-alpha
PubMed: 32847845
DOI: 10.1136/gutjnl-2020-322129 -
Annual Review of Immunology Apr 2017Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but... (Review)
Review
Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases.
Topics: Animals; Biological Therapy; Brain; Central Nervous System; Cytokines; Homeostasis; Humans; Microglia; Neurodegenerative Diseases; Neurogenic Inflammation
PubMed: 28226226
DOI: 10.1146/annurev-immunol-051116-052358 -
International Journal of Molecular... Oct 2021Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new... (Review)
Review
Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new therapies that have contributed to the advances in treatment of certain malignancies. Immunotherapy, which has repeatedly proven to be a breakthrough therapy in melanoma, as well as B-ALL therapy with CAR T cells, are of great merit in this progress. These therapies are currently being developed by modifying bispecific antibodies and CAR T cells to improve their efficiency and bioavailability. Work on improving the therapy with oncolytic viruses is also progressing, and efforts are being made to improve the immunogenicity and stability of cancer vaccines. Combining various biological therapies, immunotherapy with oncolytic viruses or cancer vaccines is gaining importance in cancer therapy. New therapeutic targets are intensively sought among neoantigens, which are not immunocompromised, or antigens associated with tumor stroma cells. An example is fibroblast activation protein α (FAPα), the overexpression of which is observed in the case of tumor progression. Universal therapeutic targets are also sought, such as the neurotrophic receptor tyrosine kinase (NTRK) gene fusion, a key genetic driver present in many types of cancer. This review also raises the problem of the tumor microenvironment. Stromal cells can protect tumor cells from chemotherapy and contribute to relapse and progression. This publication also addresses the problem of cancer stem cells resistance to treatment and presents attempts to avoid this phenomenon. This review focuses on the most important strategies used to improve the selectivity of biological therapies.
Topics: Animals; Antibodies; Biological Therapy; Cancer Vaccines; Humans; Molecular Targeted Therapy; Neoplasms; Recombinant Proteins; T-Lymphocytes
PubMed: 34769123
DOI: 10.3390/ijms222111694 -
Rheumatology (Oxford, England) Dec 2021In this review, the results of recent and ongoing clinical trials in patients with SLE are discussed. After many unsuccessful trials in the past decade, belimumab was... (Review)
Review
In this review, the results of recent and ongoing clinical trials in patients with SLE are discussed. After many unsuccessful trials in the past decade, belimumab was the first biologic specifically designed for SLE that met its primary end point. At the same time, studies on the pathophysiology of SLE have further elucidated the pathways involved in the disease, which has led to the identification of new possible therapeutics and has encouraged the initiation of new trials. These new drugs include biologics that target B cells, T cells and type 1 interferons, and small molecules that inhibit kinases. Other therapeutics aim to restore immunological balance by restoring tolerance. Results from phase II and even phase III trials are promising and it is likely that some of the therapeutics discussed will receive approval in the following years. Hopefully, this will allow for more tailor-made medicine for SLE patients in the future.
Topics: Biological Therapy; Humans; Lupus Erythematosus, Systemic
PubMed: 34951924
DOI: 10.1093/rheumatology/keab498 -
Rheumatology (Oxford, England) Dec 2021SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely... (Review)
Review
SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely empirical and offer only symptomatic relief for patients. There are no proven treatments that alter disease progression or treat the systemic manifestations of disease. B-cell depletion is used in patients with systemic disease but its overall clinical efficacy has not been demonstrated in two large randomized controlled trials. Studies are now focussing on alternative strategies to target B-cells, including co-stimulation targets, with promising data. It is increasingly clear that clinical trials in SS will require patient stratification and relevant and sensitive outcome measures to identify successful treatment modalities.
Topics: B-Lymphocytes; Biological Therapy; Humans; Sjogren's Syndrome
PubMed: 34951923
DOI: 10.1093/rheumatology/keab466 -
Frontiers in Cellular and Infection... 2017is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of... (Review)
Review
is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant , few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of is important. In this review, we summarize current studies on the virulence factors that contribute to pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant are summarized.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Biological Therapy; Drug Resistance, Multiple, Bacterial; Humans; Virulence Factors
PubMed: 28348979
DOI: 10.3389/fcimb.2017.00055