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Immunomodulatory therapy

Daniel S Chen, Herbert Hurwitz
Cancer immunotherapy (CIT) has transformed cancer treatment. In particular, immunotherapies targeting the programmed death ligand 1 (PD-L1)/programmed death 1 pathway have demonstrated durable clinical benefit in some patients. However, CIT combinations may create a more favorable environment in which to maximize the potential of the immune system to eliminate cancer. Here we describe 3 key mechanisms related to vascular endothelial growth factor (VEGF)-mediated immunosuppression: inhibition of dendritic cell maturation, reduction of T-cell tumor infiltration, and promotion of inhibitory cells in the tumor microenvironment; supporting data are also described...
July 2018: Cancer Journal
Hannah Smith, Ruth Forman, Iris Mair, Kathryn J Else
Macrophages represent a highly heterogeneous and plastic cell type found in most tissues of the body; the intestine is home to enormous numbers of these cells. Considerable interest surrounds the 'M2 macrophage,' as it is able to control and regulate inflammation, while promoting tissue repair. Areas covered: As potent inducers of M2 macrophages, intestinal helminths and helminth-derived products are ideal candidates for small molecule drug design to drive M2 macrophage polarization. Several gastrointestinal helminths have been found to cause M2 macrophage-inducing infections...
August 16, 2018: Expert Review of Gastroenterology & Hepatology
Emily K Sims, Carmella Evans-Molina, Sarah A Tersey, Decio L Eizirik, Raghavendra G Mirmira
Recent work on the pathogenesis of type 1 diabetes has led to an evolving recognition of the heterogeneity of this disease, both with regards to clinical phenotype and responses to therapies to prevent or revert diabetes. This heterogeneity not only limits efforts to accurately predict clinical disease but also is reflected in differing responses to immunomodulatory therapeutics. Thus, there is a need for robust biomarkers of beta cell health, which could provide insight into pathophysiological differences in disease course, improve disease prediction, increase the understanding of therapeutic responses to immunomodulatory interventions and identify individuals most likely to benefit from these therapies...
August 15, 2018: Diabetologia
Lluís Guirado
Delayed graft function (DGF) increases the risk of graft loss by up to 40%, and recent developments in kidney donation have increased the risk of its occurrence. Lowering the risk of DGF, however, is challenging due to a complicated etiology in which ischemia-reperfusion injury (IRI) leads to acute tubular necrosis. Among various strategies explored, the choice of induction therapy is one consideration. Rabbit antithymocyte globulin (rATG [Thymoglobuline]) has complex immunomodulatory effects that are relevant to DGF...
2018: Journal of Transplantation
Lin Wei, Yang Yang, Yandong Zhou, Min Li, Hailong Yang, Lixian Mu, Qian Qian, Jing Wu, Wei Xu
BACKGROUND: Mosquitoes are armed with physiologically active compounds to suppress the host immunity including host inflammatory reaction. However, the specific anti-inflammatory components in mosquitoes remain unknown. RESULTS: By searching for the immunomodulatory molecules from the mosquito Aedes aegypti (Diptera: Culicidae) at NCBI for anti-inflammatory function, five cecropins (for short in this study: AeaeCec1, 2, 3, 4 and 5) were selected. AeaeCec1-5 efficiently inhibited the expression of inducible nitric oxide synthase (iNOS), nitrite, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages and human peripheral blood mononuclear cells (PBMCs) with low toxicity to mammalian cells...
August 14, 2018: Parasites & Vectors
Tao Zhang, Caterina De Carolis, Man Gene Chi-Wai, Chi-Chiu Wang
Endometriosis (EMS), an estrogen-dependent inflammatory disorder affects approximately 5-10% of the general female population of reproductive age and 20-90% of women with pelvic pain and infertility. Many immunological factors are known to contribute significantly to the pathogenesis and pathophysiology of EMS, and both chronic local inflammation and autoantibodies in EMS shares many similarities with autoimmune diseases (AD). However, the autoimmune etiology in EMS remains controversial, and its evidence on autoimmune basis may be limited...
August 11, 2018: Autoimmunity Reviews
Hua Wang, David J Mooney
The past decade has witnessed the accelerating development of immunotherapies for cancer treatment. Immune checkpoint blockade therapies and chimeric antigen receptor (CAR)-T cell therapies have demonstrated clinical efficacy against a variety of cancers. However, issues including life-threatening off-target side effects, long processing times, limited patient responses and high cost still limit the clinical utility of cancer immunotherapies. Biomaterial carriers of these therapies, though, enable one to troubleshoot the delivery issues, amplify immunomodulatory effects, integrate the synergistic effect of different molecules and, more importantly, home and manipulate immune cells in vivo...
August 13, 2018: Nature Materials
Yi-Heng Lin, Ya-Hsin Chen, Heng-Yu Chang, Heng-Kien Au, Chii-Ruey Tzeng, Yen-Hua Huang
Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects...
August 13, 2018: International Journal of Molecular Sciences
Moellmann Julia, Klinkhammer Barbara Mara, Onstein Julia, Stöhr Robert, Jankowski Vera, Jankowski Joachim, Lebherz Corinna, Tacke Frank, Marx Nikolaus, Boor Peter, Lehrke Michael
Incretin based therapies, including GLP-1 receptor agonists and dipeptidylpeptidase 4 (DPP-4) inhibitors, are potent glucose lowering drugs. Still, only GLP-1 receptor agonists with close peptide homology to GLP-1 (liraglutide and semaglutide) but neither exenatide based GLP-1 receptor agonists nor DPP-4 inhibitors were found to reduce cardiovascular events. This different response might relate to GLP-1 receptor independent actions of GLP-1 caused by cleavage products only liberated by GLP-1 receptor agonists with close peptide structure to GLP-1...
August 13, 2018: Diabetes
Leslie Padrnos, Brenda Ernst, Amylou C Dueck, Heidi E Kosiorek, Brenda F Ginos, Angela Toro, Patrick B Johnston, Thomas M Habermann, Jose F Leis, Joseph R Mikhael, Grzegorz S Nowakowski, Joseph Colgan, Luis Porrata, Stephen M Ansell, Thomas E Witzig, Craig Reeder
BACKGROUND: Treatment outcomes have improved in lymphoid malignancies but relapse remains inevitable for most patients. Everolimus and lenalidomide have shown clinical activity as single agents in patients with relapsed and refractory Hodgkin and non-Hodgkin lymphomas. PATIENTS AND METHODS: The present phase I/II trial for patients with relapsed and refractory lymphoid malignancy opened at Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3 design to determine the maximum tolerated dose for the combination...
June 15, 2018: Clinical Lymphoma, Myeloma & Leukemia
Kiyoshi Okazuka, Tadao Ishida
Therapeutic strategies for multiple myeloma have dramatically changed in the last two decades, especially after the introduction of proteasome inhibitors. The first-in-class proteasome inhibitor, bortezomib, was approved by the US Food and Drug Administration in 2003. Since then, it has been a backbone therapy for not only relapsed or refractory myeloma patients but also newly diagnosed multiple myeloma patients. Second-generation proteasome inhibitors, such as carfilzomib and ixazomib, have been approved, and three proteasome inhibitors were incorporated into several regimens with other cytotoxic agents, such as alkylating agents, immunomodulatory drugs and monoclonal antibodies...
August 9, 2018: Japanese Journal of Clinical Oncology
Yiyi Yan, Anagha Bangalore Kumar, Heidi Finnes, Svetomir N Markovic, Sean Park, Roxana S Dronca, Haidong Dong
Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. However, primary or acquired therapy resistance can affect up to two-thirds of patients receiving ICIs, underscoring the urgency to elucidate the mechanisms of treatment resistance and to design more effective therapeutic strategies. Conventional cancer treatments, including cytotoxic chemotherapy, radiation therapy, and targeted therapy, have immunomodulatory effects in addition to direct cancer cell-killing activities...
2018: Frontiers in Immunology
Rachel Bender Ignacio, Lilie L Lin, Lakshmi Rajdev, Elizabeth Chiao
This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non-AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies...
August 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Fanwen Wang, Caoying Xu, Renhao Peng, Bin Li, Xutong Shen, Heng Zheng, Xingzhen Lao
Thymosin α1 (Tα1), a hormone containing 28 amino acids, has been approved in several cancer therapies, but the lack of tumor-targeting hinders its full use in tumor treatment. We designed a new peptide by connecting Tα1 and RGDR, generating a product, Tα1-RGDR, where RGDR is located in the C-end with both tumor-homing and cell internalizing properties (C-end rule peptides, a consensus R/KXXR/K motif). This work aimed to study the antitumor and immunological activities of Tα1-RGDR, and its differences compared with the wild-type Tα1...
August 7, 2018: Biochimie
Faye A Sharpley, Richa Manwani, Shameem Mahmood, Sajitha Sachchithanantham, Helen Lachmann, Julian Gilmore, Carol Whelan, Phillip Hawkins, Ashutosh Wechalekar
Pomalidomide is a next-generation immunomodulatory agent with activity in relapsed light chain (AL) amyloidosis, but real world outcomes are lacking. We report the experience of the UK National Amyloidosis Centre. All patients with AL amyloidosis treated with pomalidomide between 2009 and 2017 were included. Data was collected on treatment toxicity and clonal response. Survival was calculated by the Kaplan-Meier method and outcomes reported on an intent-to-treat (ITT) basis. A total of 29 patients treated with pomalidomide were identified...
August 10, 2018: British Journal of Haematology
Fu Yuan Yang, Rui Chen, Xiaohu Zhang, Biao Huang, Lai Ling Tsang, Xican Li, Xiaohua Jiang
Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration...
August 10, 2018: Cell Transplantation
Cristy Phillips, Atoossa Fahimi
Physical activity-a lifestyle factor that is associated with immune function, neuroprotection, and energy metabolism-modulates the cellular and molecular processes in the brain that are vital for emotional and cognitive health, collective mechanisms that can go awry in depression. Physical activity optimizes the stress response, neurotransmitter level and function (e.g., serotonergic, noradrenergic, dopaminergic, and glutamatergic), myokine production (e.g., interleukin-6), transcription factor levels and correlates [e...
2018: Frontiers in Neuroscience
Eric Grignano, Vincent Jachiet, Pierre Fenaux, Lionel Ades, Olivier Fain, Arsène Mekinian
Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger patients with higher risk IPSS. MDS subtypes associated with ADs are mainly MDS with single lineage dysplasia (MDS-SLD) and MDS with excess blasts (MDS-EB). Various types of ADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities as vasculitis, connective tissue diseases, inflammatory arthritis, and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can be seen...
August 8, 2018: Annals of Hematology
Qi Hui Sam, Wen Shan Yew, Chaminda J Seneviratne, Matthew Wook Chang, Louis Yi Ann Chai
Invasive fungal disease (IFD) causes significant morbidity in immunocompromised patients due to their weakened immune system. Immunomodulatory therapy, in synergy with existing antifungal therapy, is an attractive option to enhance their immune system and aid clearance of these opportunistic pathogens. From a scientific and clinical perspective, we explore the immunotherapeutic options to augment standard antifungal drugs for patients with an IFD. We discuss the range of immunomodulatory therapies being considered in IFD - from cytokines, including G-CSF, GM-CSF, M-CSF, IFN-γ, and cytokine agonists, to cellular therapies, consisting of granulocyte transfusion, adoptive T-cell, CAR T-cell, natural killer cell therapies, and monoclonal antibodies...
2018: Frontiers in Microbiology
Kazuya Kobayashi, Ken Suzuki
Transplantation of stem/progenitor cells is a promising, emerging treatment for heart failure (HF) in the modern era. Mesenchymal stem/stromal cells (MSCs) are considered as one of the most promising cell sources for this purpose, because of their powerful secretion of reparative factors and immunomodulatory ability. To date, various sources of MSCs have been examined for the treatment of HF in preclinical or clinical studies, including adult tissues (bone marrow and adipose tissue), perinatal tissues (umbilical cord and amnion), and pluripotent stem cells (induced pluripotent stem cells and embryonic stem cells)...
August 9, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
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