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https://www.readbyqxmd.com/read/29792730/nivolumab-for-the-treatment-of-colorectal-cancer
#1
Kortnye Maureen Smith, Jayesh Desai
Despite a variety of therapies for advanced metastatic colorectal cancer being available, the outcomes in this malignancy remain sub-optimal. Immunotherapy has been slow to impact the management of this patient group. Checkpoint inhibitors, such as nivolumab, have had disappointing results when used broadly. However, for the subset of patients with microsatellite unstable colorectal cancer the use of checkpoint inhibitors such as nivolumab appears to be transformative, and will provide a new therapeutic option for patient with advanced disease...
May 24, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29792670/biomarker-based-metabolic-labeling-for-redirected-and-enhanced-immune-response
#2
Shanshan Li, Bingchen Yu, Jiajia Wang, Yueqin Zheng, Huajie Zhang, Margaret J Walker, Zhengnan Yuan, He Zhu, Jun Zhang, Peng George Wang, Binghe Wang
Installation of an antibody-recruiting moiety on the surface of disease-relevant cells can lead to the selective destruction of targets by the immune system. Such an approach can be an alternative strategy to traditional chemotherapeutics in cancer therapy and possibly other diseases. Herein we describe the development of a new strategy to selectively label targets with an antibody-recruiting moiety through its covalent and stable installation, complementing existing methods of employing reversible binding...
May 24, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29791948/multiple-sclerosis
#3
Bassem I Yamout, Raed Alroughani
Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune etiology, mediated by activated T cells with evolving evidence of a significant contribution from B cells and cells of the innate immune system. The disease is thought to be due to a complex interaction between different genetic and environmental factors. The prevalence of MS is rising all over the world, due on one hand to earlier diagnosis and prolonged survival, and on the other to a true increase in incidence of the disease...
April 2018: Seminars in Neurology
https://www.readbyqxmd.com/read/29791878/computational-design-of-antibodies
#4
REVIEW
Sharon Fischman, Yanay Ofran
Antibody design aims to create new antibodies with biological activity that can be used in therapy and research. Traditional methods for antibody discovery, such as animal immunization and large-scale library screening, generate antibodies that bind to the target of interest, but do not necessarily have the desired functional effect. Computational methods can be utilized as a means to guide the search for biologically relevant antibodies, focusing on specificity and affinity determinants to target a particular region of the antigen...
May 19, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29791768/vaccine-immunotherapy-with-arnax-induces-tumor-specific-memory-t-cells-and-durable-anti-tumor-immunity-in-mouse-models
#5
Yohei Takeda, Sumito Yoshida, Ken Takashima, Noriko Ishii-Mugikura, Hiroaki Shime, Tsukasa Seya, Misako Matsumoto
Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with TLR3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In this study, four different OVA-expressing tumor cell lines were implanted into syngeneic mice and subjected to antitumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a Toll-like receptor 3-specific agonist that does not activate the MAVS pathway, and thus does not induce systemic inflammation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29791021/immtac-anti-pd-1-combination-to-enhance-killing-of-cancer-cells-by-reversing-treg-mediated-immunosuppression
#6
Huanling Zhang, Yanyan Li, Xiaoping Liu, Zhaoduan Liang, Mengyong Yan, Qiang Liu, Anan Chen, Yifeng Bao, Chengzhi Zhou, Shiyue Li, Cassian Yee, Yi Li
Recently, bi-functional molecules that can redirect immune effectors to tumor cells have emerged as potentially robust mediators of tumor regression in clinical trials. Two modalities, in particular, bi-specific antibodies for T cell redirection and activation (BiTe) and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC) are being evaluated in efficacy studies as 'off-the-shelf' reagents. Optimal therapy will require an understanding and means to address regulatory mechanisms of limiting efficacy...
May 23, 2018: Immunology
https://www.readbyqxmd.com/read/29791013/frontline-science-buprenorphine-decreases-ccl2-mediated-migration-of-cd14-cd16-monocytes
#7
Matias Jaureguiberry-Bravo, Lillie Lopez, Joan W Berman
HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB)...
May 23, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29790966/tcrmodel-high-resolution-modeling-of-t-cell-receptors-from-sequence
#8
Ragul Gowthaman, Brian G Pierce
T cell receptors (TCRs), along with antibodies, are responsible for specific antigen recognition in the adaptive immune response, and millions of unique TCRs are estimated to be present in each individual. Understanding the structural basis of TCR targeting has implications in vaccine design, autoimmunity, as well as T cell therapies for cancer. Given advances in deep sequencing leading to immune repertoire-level TCR sequence data, fast and accurate modeling methods are needed to elucidate shared and unique 3D structural features of these molecules which lead to their antigen targeting and cross-reactivity...
May 22, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29790481/antiviral-combination-therapy-for-cytomegalovirus-infection-in-high-risk-infants
#9
Surabhi B Vora, Adam W Brothers, Alpana Waghmare, Janet A Englund
BACKGROUND: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear...
May 23, 2018: Antiviral Therapy
https://www.readbyqxmd.com/read/29790392/interleukin-1-receptor-il-1r1-activation-exacerbates-toxin-induced-acute-kidney-injury
#10
Jamie R Privratsky, Jiandong Zhang, Xiaohan Lu, Nathan Rudemiller, Qingqing Wei, Yen-Rei Yu, Michael Dee Gunn, Steven D Crowley
Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Cisplatin is an effective chemotherapeutic agent whose administration is limited by nephrotoxicity. Therapies to prevent cisplatin-induced AKI are lacking. While tumor necrosis factor-α (TNF) plays a key role in the pathogenesis of cisplatin nephrotoxicity, the immune signaling pathways that trigger TNF generation in this context require elucidation. Sterile injury triggers the release and activation of both isoforms of interleukin(IL)-1, IL-1α and IL-1β, and stimulation of the interleukin-1 receptor (IL-1R1) by these ligands engages a pro-inflammatory signaling cascade that induces TNF induction...
May 23, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29790193/myasthenic-ophthalmoparesis-time-to-resolution-after-initiating-immune-therapies
#11
T A Europa, M Nel, J M Heckmann
INTRODUCTION: Although immunotherapies such as prednisone are effective in treating myasthenic muscle weakness, their effect on resolution of myasthenic-induced persistent ophthalmoparesis is unknown. METHODS: We observed myasthenia gravis patients during their first year of immunotherapy, documenting ophthalmoplegia scores and drug doses. RESULTS: Seventy-six of 87 cases had persistent ophthalmoparesis. On immunotherapy, the median time to resolution of ophthalmoparesis was 7 months and 37% resolved within 3 months...
May 23, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29789655/cigarette-smoke-promotes-hiv-infection-of-primary-bronchial-epithelium-and-additively-suppresses-cftr-function
#12
S Chinnapaiyan, R Dutta, J Bala, T Parira, M Agudelo, M Nair, H J Unwalla
Recurrent lung infections are a common cause of morbidity and mortality in people living with HIV and this is exacerbated in smokers even when administered combination antiretroviral therapy (cART). The incidence of pneumonia is increased with smoking and treatment interruption and is directly dependent on viral load in patients when adjusted for CD4 counts. CFTR dysfunction plays an important role in aberrant airway innate immunity as it is pivotal in regulating mucociliary clearance (MCC) rates and other antibacterial mechanisms of the airway...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789418/juxtacrine-signaling-inhibits-antitumor-immunity-by-upregulating-pd-l1-expression
#13
Wen-Hao Yang, Jong-Ho Cha, Weiya Xia, Heng-Huan Lee, Li-Chuan Chan, Ying-Nai Wang, Jennifer L Hsu, Guoxin Ren, Mien-Chie Hung
Programmed death-ligand 1 (PD-L1) is a well-known immune checkpoint protein that helps cancer cells evade immune response. Anti-PD-L1 immune therapy has been approved for the treatment of several advanced human cancers. Therefore, further understanding of the regulatory mechanisms of PD-L1 is critical to improve PD-L1-targeting immunotherapy. Recent studies indicated that contact-dependent pathways may regulate anticancer immunity, highlighting the importance of cell contact-induced signaling in cancer immunity...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29789416/macrophage-derived-granulin-drives-resistance-to-immune-checkpoint-inhibition-in-metastatic-pancreatic-cancer
#14
Michael C Schmid, Valeria Quaranta, Carolyn Rainer, Sebastian Rune Nielsen, Meirion Llŷr Raymant, Muhammad S Ahmed, Dannielle D Engle, Arthur Taylor, Trish Murray, Fiona Campbell, Daniel H Palmer, David A Tuveson, Ainhoa Mielgo
The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study we find that macrophage-derived granulin contributes to cytotoxic CD8+ T cell exclusion in metastatic livers...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29789350/regulatory-t-cells-and-kidney-transplantation
#15
REVIEW
Paloma Leticia Martin-Moreno, Sudipta Tripathi, Anil Chandraker
The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection...
May 22, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29788960/ecto-5-nucleotidase-cd73-attenuates-inflammation-after-spinal-cord-injury-by-promoting-macrophages-microglia-m2-polarization-in-mice
#16
Shun Xu, Wei Zhu, Minghao Shao, Fan Zhang, Ji Guo, Haocheng Xu, Jianyuan Jiang, Xiaosheng Ma, Xinlei Xia, Xiuling Zhi, Ping Zhou, Feizhou Lu
BACKGROUND: Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states-the classically activated M1 phenotype that confers pro-inflammatory effects or the alternatively activated M2 phenotype that confers anti-inflammatory effects. Ecto-5'-nucleotidase (CD73) is an immunosuppressive molecule intricately involved in adaptive and innate immune responses and is able to dephosphorylate AMP to adenosine...
May 22, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29788907/mycobacterium-avium-complex-vertebral-osteomyelitis-in-the-absence-of-hiv-infection-a-case-report-and-review
#17
Megan E Gray, Peter W Liu, Brian Wispelwey
BACKGROUND: Mycobacterium Avium Complex (MAC) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. However, MAC manifesting as vertebral osteomyelitis is less common, and is particularly rare in the absence of Acquired Immunodeficiency Syndrome (AIDS). Prompt diagnosis of MAC vertebral osteomyelitis is challenging, but necessary to prevent serious morbidity or mortality. CASE PRESENTATION: We report a case of MAC osteomyelitis of the lumbar spine in a 70-year-old woman on extended duration corticosteroid therapy for systemic lupus erythematosus who presented with progressive back pain...
May 22, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29788841/heparin-induced-thrombocytopenia-complicating-extracorporeal-membrane-oxygenation-support-in-pediatric-patients-review-of-the-literature-and-alternative-anticoagulants
#18
Uri Pollak
Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated complication of unfractionated heparin (UFH) and low molecular weight heparin therapy. HIT is characterized by moderate thrombocytopenia 5-10 days after initial heparin exposure, detection of platelet-activating anti-platelet factor 4/heparin antibodies and an increased risk of venous and arterial thrombosis. Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulatory support used in critically ill patients with respiratory or cardiac failure...
May 2018: Perfusion
https://www.readbyqxmd.com/read/29788675/anti-tumor-necrosis-factor-therapy-in-intestinal-beh%C3%A3-et-s-disease
#19
REVIEW
Jihye Park, Jae Hee Cheon
Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor α, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating...
May 24, 2018: Gut and Liver
https://www.readbyqxmd.com/read/29788474/umbilical-cord-blood-transplantation-corrects-very-early-onset-inflammatory-bowel-disease-in-chinese-patients-with-il10ra-associated-immune-deficiency
#20
Kaiyue Peng, Xiaowen Qian, Zhiheng Huang, Junping Lu, Yuhuan Wang, Ying Zhou, Huijun Wang, Bingbing Wu, Ying Wang, Lingli Chen, Xiaowen Zhai, Ying Huang
Background: Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. Methods: We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing...
May 18, 2018: Inflammatory Bowel Diseases
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