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Immunomodulatory agents

Ronald F van Vollenhoven
The autoimmune rheumatological diseases rheumatoid arthritis (RA), spondyloarthritis (SpA) and systemic lupus erythematosus (SLE) are treated with conventional immunosuppressive agents and with modern biological immunomodulators. The latter group of medications have brought about a major change in our ability to control RA and SpA, with more modest results for SLE. The biologicals are very specific in their mechanisms of action, targeting one specific cytokine or one particular cellular marker. Because of this, their efficacy can readily be linked to a single immunomodulatory mechanism...
June 16, 2018: Journal of Internal Medicine
Parameswaran Hari, Donna E Reece, Jasleen Randhawa, Neal Flomenberg, Dianna S Howard, Ashrof Z Badros, Aaron P Rapoport, Barry R Meisenberg, Joanne Filicko-Ohara, Gordon L Phillips, David H Vesole
The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m2 (MEL 200). Higher doses of melphalan 220-260 mg/m2 , although relatively well tolerated, have not shown significant improvement in clinical outcomes. Several approaches have been pursued in the past to improve CR rates, including poly-chemotherapy preparative regimens, tandem ASCT, consolidation, and/or maintenance therapy. Since there is a steep dose-response effect for intravenous melphalan, we evaluated an alternative single ASCT strategy using higher-dose melphalan at 280 mg/m2 (MEL 280) with amifostine as a cytoprotectant as the maximum tolerated dose determined in an earlier phase I dose escalation trial...
June 15, 2018: Bone Marrow Transplantation
Alexander T Baker, Carmen Aguirre-Hernández, Gunnel Halldén, Alan L Parker
The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability...
June 14, 2018: Cancers
Anna T Wilmes, Sabrina Reinehr, Sandra Kühn, Xiomara Pedreiturria, Laura Petrikowski, Simon Faissner, Ilya Ayzenberg, Gesa Stute, Ralf Gold, H Burkhard Dick, Ingo Kleiter, Stephanie C Joachim
BACKGROUND: The oral immunomodulatory agent laquinimod is currently evaluated for multiple sclerosis (MS) treatment. Phase II and III studies demonstrated a reduction of degenerative processes. In addition to anti-inflammatory effects, laquinimod might have neuroprotective properties, but its impact on the visual system, which is often affected by MS, is unknown. The aim of our study was to investigate potential protective effects of laquinimod on the optic nerve and retina in an experimental autoimmune encephalomyelitis (EAE) model...
June 14, 2018: Journal of Neuroinflammation
Min-Chul Kim, Sung-Cheol Yun, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Sung-Han Kim
OBJECTIVES: Statins, which are lipid-lowering agents, have anti-inflammatory and immunomodulatory properties that may affect the occurrence of various infectious diseases. We assessed whether statins increase the risk of herpes zoster (HZ) with propensity score-matching. METHODS: The study was based on the National Health Insurance database and its subset database of the "medical check-up" population of South Korea. These cohorts consist of about one million and 570,000 people, respectively, representative of the entire population of South Korea...
2018: PloS One
Anna Zanfardino, Andrea Bosso, Giovanni Gallo, Valeria Pistorio, Michela Di Napoli, Rosa Gaglione, Eliana Dell'Olmo, Mario Varcamonti, Eugenio Notomista, Angela Arciello, Elio Pizzo
Bioactive peptides derived from the receptor-binding region of human apolipoprotein E have previously been reported. All these peptides, encompassing fragments of this region or designed on the basis of short repeated cationic sequences identified in the same region, show toxic activities against a broad spectrum of bacteria and interesting immunomodulatory effects. However, the ability of these molecules to exert antibiofilm properties has not been described so far. In the present work, we report the characterization of a novel peptide, corresponding to residues 133 to 167 of human apolipoprotein E, here named ApoE (133-167)...
June 14, 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
Tian Zhou, Zijing Huang, Xiaowei Zhu, Xiaowei Sun, Yan Liu, Bing Cheng, Mei Li, Yizhi Liu, Chang He, Xialin Liu
Neurodegenerative diseases are a set of disorders characterized by progressive neuronal death and are associated with microglia-mediated neuroinflammation. Recently, neuroinflammation is proposed as a promising therapeutic target for many neurodegenerative diseases. Alpha-1 antitrypsin (AAT) is recognized as a novel immunomodulatory agent in autoimmune diseases and transplantation, however, its impact on neuroinflammation and neurodegeneration remains unknown. This study aims to explore the effects of AAT on microglia-mediated neuroinflammation and retinal degeneration in rd1 mouse model...
2018: Frontiers in Immunology
Edward Hammond, Nicole M Haynes, Carleen Cullinane, Todd V Brennan, Darryn Bampton, Paul Handley, Tomislav Karoli, Fleur Lanksheer, Liwen Lin, Yiping Yang, Keith Dredge
BACKGROUND: Pixatimod (PG545) is a novel clinical-stage immunomodulatory agent capable of inhibiting the infiltration of tumor-associated macrophages (TAMs) yet also stimulate dendritic cells (DCs), leading to activation of natural killer (NK) cells. Preclinically, pixatimod inhibits heparanase (HPSE) which may be associated with its inhibitory effect on TAMs whereas its immunostimulatory activity on DCs is through the MyD88-dependent TLR9 pathway. Pixatimod recently completed a Phase Ia monotherapy trial in advanced cancer patients...
June 14, 2018: Journal for Immunotherapy of Cancer
Rong Zhou, Zhaokun Liu, Yeni N Zhang, Tzi Bun Ng, Fang Liu
For centuries, mushrooms have been widely used as traditional Chinese medicine in Asia. Apart from polysaccharides and some small-molecule components, such as flavones, ployphenols and terpenes, mushrooms produce a large number of pharmaceutically active proteins, which have become popular sources of natural antitumor, antimicrobial, immunoenhancing agents. These bioactive proteins include lectins, laccases, ribosome inactivating proteins (RIPs), nucleases, and fungal immunomodulatory proteins (FIPs). The review is to summarize the characters of structure and bioactivities involved in antitumor, antiviral, antifungal, antibacterial and immunoenhancing activities of proteins from edible mushrooms, to better understand their mechanisms, and to direct research...
June 12, 2018: Current Protein & Peptide Science
Ayesha Obaid, Anam Naz, Aqsa Ikram, Faryal Mehwish Awan, Abida Raza, Jamil Ahmad, Amjad Ali
A regulated immune system employs multiple cell types, diverse variety of cytokines and interacting signalling networks against infections. Systems biology offers a promising solution to model and simulate such large populations of interacting components of immune systems holistically. This study focuses on the distinct components of the adaptive immune system and analysis, both individually and in association with HCV infection. The effective and failed adaptive immune response models have been developed followed by interventions/perturbations of various treatment strategies to get better assessment of the treatment responses under varying stimuli...
June 11, 2018: Scientific Reports
Zijian Li, Yue You, Noreen Griffin, Juan Feng, Fengping Shan
Naltrexone, a non-selective antagonist of opioid receptors, is mainly used as rehabilitation therapy for discharged opiate addicts to eliminate addiction in order to maintain a normal life and prevent or reduce relapse. In recent years, there have been some novel and significant findings on the off-label usage of naltrexone. Within a specific dosage window, LDN can act as an immunomodulator in multiple autoimmune diseases and malignant tumors as well as alleviate the symptoms of some mental disorders. The results of increasing studies indicate that LDN exerts its immunoregulatory activity by binding to opioid receptors in or on immune cells and tumor cells...
June 6, 2018: International Immunopharmacology
Eun-Young Choi, So-Hui Choe, Jin-Yi Hyeon, Hae Ryoun Park, In Soon Choi, Sung-Jo Kim
AIMS: Josamycin has immunomodulatory properties independent of its antibacterial actions. This study was designed to explore the influences and associated mechanisms of josamycin upon the generation of proinflammatory mediators in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogenic bacterium associated with periodontal disease. MAIN METHODS: LPS was purified by employing phenol-water extraction protocol. Culture supernatants were analyzed for nitric oxide (NO) and interleukin (IL)-1β...
June 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Manon Bosseler, Vanessa Marani, Angelina Broukou, Amandine Lequeux, Tony Kaoma, Vincent Schlesser, Jean-Hugues François, Valérie Palissot, Guy J Berchem, Nasséra Aouali, Bassam Janji
The introduction of novel frontline agents in multiple myeloma (MM), like immunomodulatory drugs and proteasome inhibitors, has improved the overall survival of patients. Yet, MM is still not curable, and drug resistance (DR) remains the main challenge. To improve the understanding of DR in MM, we established a resistant cell line (MOLP8/R). The exploration of DR mechanisms yielded an overexpression of HIF1α, due to impaired proteasome activity of MOLP8/R. We show that MOLP8/R, like other tumor cells, overexpressing HIF1α, have an increased resistance to the immune system...
May 23, 2018: International Journal of Molecular Sciences
L Peyton Myers
Assessment of the potential for a test article to have adverse effects on immune function can be difficult in clinical trials due to a relative lack of useful endpoints. It is therefore common to use a weight of evidence approach with nonclinical studies to indicate if there is a cause for concern that the test article has immunotoxic potential. The most commonly used follow-up assay for immunosuppression is the T-dependent antibody response (TDAR). However, final selection of an assay (or assays) to evaluate potential human immunotoxicity depends on the type of findings in nonclinical studies...
2018: Methods in Molecular Biology
Seyed Shahabeddin Mortazavi-Jahromi, Mahsa Taeb, Salvatore Cuzzocrea, Emanuela Esposito
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat the pathological pain and inflammation through inhibition of cyclooxygenase (COX) enzyme and disruption of the synthesis of prostaglandins (PGs). The α-L-guluronic acid (G2013) patented (PCT/EP2017/067920), as a novel NSAID with the immunomodulatory property, has been shown its positive effects in experimental models of multiple sclerosis and anti-aging. OBJECTIVE: This study was aimed to investigate the effects of G2013 on the gene expression and activity of COX-1/COX-2 enzymes in order to introduce a novel NSAID for the treatment of inflammatory diseases...
June 7, 2018: Recent Patents on Inflammation & Allergy Drug Discovery
Kahori Morino, Yuichi Honma, Shinsuke Kumei, Tatsuyuki Watanabe, Keiichiro Kume, Ichiro Yoshikawa, Masaru Harada
Cronkhite-Canada syndrome (CCS) is a rare non-inherited disease characterized by gastrointestinal polyposis, chronic diarrhea, ectodermal dysplasia, skin hyperpigmentation, hair loss and nail atrophy. Although the efficacy of corticosteroid and immunomodulatory agents has been demonstrated, no standard therapy regimen has been established, and the prognosis of CCS is still poor due to various complications. We here in report a CCS patient complicated with severe sepsis and disseminated intravascular coagulation who was successfully treated by combined modality therapies, including recombinant human soluble thrombomodulin...
June 6, 2018: Internal Medicine
Ichiro Hanamura, Shinsuke Iida
Proteasome inhibitors and immunomodulatory drugs have substantially improved the clinical outcomes in patients with multiple myeloma (MM) since 2000. In 2015, the new monoclonal antibodies, daratumumab and elotuzumab, were approved for treating relapsed and/or refractory MM (RRMM). Furthermore, venetoclax, a selective BCL-2 inhibitor, and chimeric antigen receptor (CAR) T-cell therapy that work against B-cell maturation antigen (BCMA) have reportedly shown great efficacy in phase 1 studies. The efficacy of venetoclax has been observed in RRMM with t (11;14) and higher BCL-2/BCL-XL expression...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Klaudia T Warzecha, Matthias Bartneck, Diana Möckel, Lia Appold, Can Ergen, Wáel Al Rawashdeh, Felix Gremse, Patricia M Niemietz, Willi Jahnen-Dechent, Christian Trautwein, Fabian Kiessling, Twan Lammers, Frank Tacke
Poly n -butylcyanoacrylate (PBCA)-based hard-shell microbubbles (MB) have manifold biomedical applications, including targeted drug delivery or contrast agents for ultrasound (US)-based liver imaging. MB and their fragments accumulate in phagocytes, especially in the liver, but it is unclear if MB affect the function of these immune cells. We herein show that human primary monocytes internalize different PBCA-MB by phagocytosis, which transiently inhibits monocyte migration in vertical chemotaxis assays and renders monocytes susceptible to cytotoxic effects of MB during US-guided destruction...
May 2018: Advanced Biosystems
Jeffrey M H Liu, Xiaomin Zhang, Shelby Joe, Xunrong Luo, Lonnie D Shea
Introduction: The development of novel immunomodulatory strategies that might decrease the need for systemic immune suppression would greatly enable the utility of cell-based therapies. Cell transplantation on biomaterial scaffolds offers a unique opportunity to engineer a site to locally polarize immunogenic antigen generation. Herein, we investigated the localized delivery of IL-33, which is a novel cytokine that has been shown to have beneficial immunomodulatory effects in certain transplant models as mediating anti-inflammatory properties in the adipose tissue, to determine its feasibility for use as an immunomodulatory agent...
March 2018: Journal of immunology and regenerative medicine
Batool F Kirmani, Donald Barr, Diana Mungall Robinson, Zachary Pranske, Ekokobe Fonkem, Jared Benge, Jason H Huang, Geoffrey Ling
Status epilepticus is a neurological emergency with increased morbidity and mortality. Urgent diagnosis and treatment are crucial to prevent irreversible brain damage. In this mini review, we will discuss the recent advances in the diagnosis and treatment of autoimmune status epilepticus (ASE), a rare form of the disorder encountered in the intensive care unit. ASE can be refractory to anticonvulsant therapy and the symptoms include subacute onset of short-term memory loss with rapidly progressive encephalopathy, psychiatric symptoms with unexplained new-onset seizures, imaging findings, CSF pleocytosis, and availability of antibody testing makes an earlier diagnosis of ASE possible...
2018: Frontiers in Neurology
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