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ImmunoTargets and Therapy

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https://www.readbyqxmd.com/read/29719818/william-bradley-coley-md-and-the-phenomenon-of-spontaneous-regression
#1
REVIEW
Leonard F Vernon
The standard definition of spontaneous regression (SR) of cancer is as follows, "…when a malignant tumor partially or completely disappears without treatment or in the presence of therapy which is considered inadequate to exert a significant influence on neoplastic disease." SR is also known as Saint Peregrine tumor, the name taken from a young priest, Peregrine Laziosi (1260 [5]-1345, exact date is unknown), who had been diagnosed with a tumor of the tibia. The mass eventually grew so large that it broke through the skin and became severely infected...
2018: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/29692982/oncogenes-in-immune-cells-as-potential-therapeutic-targets
#2
REVIEW
Gulnur K Zakiryanova, Sarah Wheeler, Michael R Shurin
The role of deregulated expression of oncogenes and tumor-suppressor genes in tumor development has been intensively investigated for decades. However, expression of oncogenes and their potential role in immune cell defects during carcinogenesis and tumor progression have not been thoroughly assessed. The defects in proto-oncogenes have been well documented and evaluated mostly in tumor cells, despite the fact that proto-oncogenes are expressed in all cells, including cells of the immune system. In this review, key studies from immune-mediated diseases that may be associated with oncogene signaling pathways are refocused to provide groundwork for beginning to understand the effects of oncogenes in and on the cancer-related immune system dysfunction...
2018: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/29535979/immunotherapy-in-merkel-cell-carcinoma-role-of-avelumab
#3
REVIEW
Amruth R Palla, Donald Doll
Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer...
2018: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/29417044/antibody-targeting-of-phosphatidylserine-for-the-detection-and-immunotherapy-of-cancer
#4
REVIEW
Olivier Belzile, Xianming Huang, Jian Gong, Jay Carlson, Alan J Schroit, Rolf A Brekken, Bruce D Freimark
Phosphatidylserine (PS) is a negatively charged phospholipid in all eukaryotic cells that is actively sequestered to the inner leaflet of the cell membrane. Exposure of PS on apoptotic cells is a normal physiological process that triggers their rapid removal by phagocytic engulfment under noninflammatory conditions via receptors primarily expressed on immune cells. PS is aberrantly exposed in the tumor microenvironment and contributes to the overall immunosuppressive signals that antagonize the development of local and systemic antitumor immune responses...
2018: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/29255699/the-current-status-of-immunobased-therapies-for-metastatic-renal-cell-carcinoma
#5
REVIEW
Niranjan J Sathianathen, Suprita Krishna, J Kyle Anderson, Christopher J Weight, Shilpa Gupta, Badrinath R Konety, Thomas S Griffith
The management of metastatic renal-cell carcinoma (mRCC) represents an important clinical challenge. Since being approved in the early 1990s, aspecific immunotherapy has been a mainstay of treatment for mRCC and the only therapy that has demonstrated long-term cures for mRCC. However, in recent times there have been landmark advances made in the field of specific immunotherapy for a number of malignancies, including kidney cancer. This review outlines the range of immunobased agents currently available for the treatment of mRCC...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/29067284/clinical-features-predictive-correlates-and-pathophysiology-of-immune-related-adverse-events-in-immune-checkpoint-inhibitor-treatments-in-cancer-a-short-review
#6
REVIEW
Jennifer M Yoest
Identification and characterization of T-cell regulatory mechanisms, or checkpoints, have led to a wave of drug development aimed at inhibiting these targets to "remove the brakes" of the immune system. This class of anticancer therapeutics, termed immune checkpoint inhibitors (ICIs), has harnessed the potential of the body's own immune system to recognize cancerous cells and selectively eliminate them, in some cases with alarming success. This new breakthrough, however, has not been without its drawbacks...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28894725/safety-of-checkpoint-inhibitors-for-cancer-treatment-strategies-for-patient-monitoring-and-management-of-immune-mediated-adverse-events
#7
REVIEW
Marianne Davies, Emily A Duffield
Immune checkpoint inhibitors (ICPIs), in the form of monoclonal antibodies against CTLA-4, PD-1, and PD-L1, have dramatically changed the treatment approach in several advanced cancers. Due to their mechanism of action, these novel agents are associated with a unique spectrum of immune-mediated adverse events (imAEs), with a safety profile that indicates they are better tolerated than traditional chemotherapeutic agents. This article aims to provide education on the current knowledge about imAEs associated with ICPI treatment, including strategies and tools for the prompt identification, evaluation, and optimal management of these events...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28670575/cd8-memory-t-cell-inflation-renders-compromised-cd4-t-cell-dependent-cd8-t-cell-immunity-via-na%C3%A3-ve-t-cell-anergy
#8
Aizhang Xu, Andrew Freywald, Yufeng Xie, Zejun Li, Jim Xiang
Whether inflation of CD8(+) memory T (mT) cells, which is often derived from repeated prime-boost vaccinations or chronic viral infections in the elderly, would affect late CD8(+) T-cell immunity is a long-standing paradox. We have previously established an animal model with mT-cell inflation by transferring ConA-stimulated monoclonal CD8(+) T cells derived from Ova-specific T-cell-receptor transgenic OTI mice into irradiation-induced lymphopenic B6 mice. In this study, we also established another two animal models with mT-cell inflation by transferring, 1) ConA-stimulated monoclonal CD8(+) T cells derived from lymphocytic choriomeningitis virus glycoprotein-specific T-cell-receptor transgenic P14 mice, and 2) ConA-stimulated polyclonal CD8(+) T cells derived from B6...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28580341/targeting-innate-immunity-to-downmodulate-adaptive-immunity-and-reverse-type-1-diabetes
#9
REVIEW
Arata Itoh, William M Ridgway
Type 1 diabetes (T1D) is characterized by specific destruction of pancreatic insulin-producing beta cells accompanied by evidence of beta-cell-directed autoimmunity such as autoreactive T cells and islet autoantibodies (IAAs). Currently, T1D cannot be prevented or reversed in humans. T1D is easy to prevent in the nonobese diabetic (NOD) spontaneous mouse model but reversing new-onset T1D in mice is more difficult. Since the discovery of the T-cell receptor in the 1980s and the subsequent identification of autoreactive T cells directed toward beta-cell antigens (eg, insulin, glutamic acid decarboxylase), the dream of antigen-specific immunotherapy has dominated the field with its promise of specificity and limited side effects...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28497030/fda-approved-immunosuppressants-targeting-staphylococcal-superantigens-mechanisms-and-insights
#10
REVIEW
Teresa Krakauer
Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic toxins cause diseases in human beings and laboratory animals by hyperactivating cells of the immune system. These protein toxins bind to the major histocompatibility complex class II (MHC II) molecules and specific Vβ regions of T-cell receptors (TCRs), resulting in the stimulation of both monocytes/macrophages and T lymphocytes. The bridging of TCR with MHC II molecules by superantigens triggers intracellular signaling cascades, resulting in excessive release of proinflammatory mediators and massive polyclonal T-cell proliferation...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28361045/phase-i-clinical-trial-of-sipuleucel-t-combined-with-escalating-doses-of-ipilimumab-in-progressive-metastatic-castrate-resistant-prostate-cancer
#11
Mark Scholz, Sabrina Yep, Micah Chancey, Colleen Kelly, Ken Chau, Jeffrey Turner, Richard Lam, Charles G Drake
BACKGROUND: Sipuleucel-T (SIP-T), which functions by stimulating cancer-specific dendritic cells, prolongs survival in men with prostate cancer. Ipilimumab (IPI) achieved a borderline survival advantage in a large randomized trial. SIP-T and IPI are potentially synergistic. PATIENTS AND METHODS: Nine men with progressive metastatic castrate-resistant prostate cancer (mCRPC) were treated prospectively with SIP-T followed immediately by IPI with one of the following doses of IPI: 1 mg/kg at 1 week after SIP-T; 1 mg/kg at 1 and 4 weeks after SIP-T; or 1 mg/kg at 1, 4, and 7 weeks after SIP-T...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28243579/first-line-treatment-of-metastatic-melanoma-role-of-nivolumab
#12
REVIEW
Jeremy Force, April Ks Salama
Historically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27785447/insights-into-the-pathogenesis-of-langerhans-cell-histiocytosis-the-development-of-targeted-therapies
#13
REVIEW
Caroline Hutter, Milen Minkov
More than a century after its first description, Langerhans cell histiocytosis (LCH) still remains an intriguing disease. Considerable progress in understanding its biology has been achieved recently. Description of the V600E BRAF mutation in samples of LCH tissue in 2010 was followed by description of additional mutations, all leading to constitutive ERK activation. Current experimental data suggest that LCH is a myeloid neoplasia with inflammatory properties, yet the exact pathophysiology remains poorly understood...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27579291/toll-like-receptors-in-the-pathogenesis-of-autoimmune-diseases-recent-and-emerging-translational-developments
#14
REVIEW
Laura Duffy, Steven C O'Reilly
Autoinflammatory diseases are defined as the loss of self-tolerance in which an inflammatory response to self-antigens occurs, which are a significant global burden. Toll-like receptors are key pattern recognition receptors, which integrate signals leading to the activation of transcription factors and ultimately proinflammatory cytokines. Recently, it has become apparent that these are at the nexus of autoinflammatory diseases making them viable and attractive drug targets. The aim of this review was to evaluate the role of innate immunity in autoinflammatory conditions alongside the role of negative regulation while suggesting possible therapeutic targets...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27529062/prion-diseases-immunotargets-and-therapy
#15
REVIEW
Jennifer T Burchell, Peter K Panegyres
Transmissible spongiform encephathalopathies or prion diseases are a group of neurological disorders characterized by neuronal loss, spongiform degeneration, and activation of astrocytes or microglia. These diseases affect humans and animals with an extremely high prevalence in some species such as deer and elk in North America. Although rare in humans, they result in a devastatingly swift neurological progression with dementia and ataxia. Patients usually die within a year of diagnosis. Prion diseases are familial, sporadic, iatrogenic, or transmissible...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27529061/the-role-of-adipokines-in-chronic-inflammation
#16
REVIEW
Peter Mancuso
Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27529060/immunotherapy-for-tuberculosis-future-prospects
#17
REVIEW
Getahun Abate, Daniel F Hoft
Tuberculosis (TB) is still a major global health problem. A third of the world's population is infected with Mycobacterium tuberculosis. Only ~10% of infected individuals develop TB but there are 9 million TB cases with 1.5 million deaths annually. The standard prophylactic treatment regimens for latent TB infection take 3-9 months, and new cases of TB require at least 6 months of treatment with multiple drugs. The management of latent TB infection and TB has become more challenging because of the spread of multidrug-resistant and extremely drug-resistant TB...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27529059/current-perspectives-on-the-immunopathogenesis-of-systemic-sclerosis
#18
REVIEW
Patrizia Fuschiotti
Systemic sclerosis (SSc or scleroderma) is a progressive and highly debilitating autoimmune disorder characterized by inflammation, vasculopathy, and extensive fibrosis. SSc is highly heterogeneous in its clinical presentation, extent and severity of skin and internal organ involvement, and clinical course and has the highest fatality rate among connective tissue diseases. While clinical outcomes have improved in recent years, no current therapy is able to reverse or slow the natural progression of SSc, a reflection of its complex pathogenesis...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27529058/current-and-emerging-treatment-options-in-the-management-of-lupus
#19
REVIEW
Natasha Jordan, David D'Cruz
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27529057/role-of-romiplostim-in-splenectomized-and-nonsplenectomized-patients-with-immune-thrombocytopenia
#20
REVIEW
Jose Perdomo
Romiplostim is a thrombopoietin receptor agonist (TPO-RA) used for the treatment of adult primary immune thrombocytopenia (ITP). ITP is an autoimmune condition characterized by low platelet counts due to increased destruction and reduced platelet production. First-line interventions include corticosteroids, anti-D, and intravenous immunoglobulins, while second-line therapies comprise splenectomy, rituximab, cyclosporine A, and TPO-RAs. The recognition that compromised platelet production is a critical part of the pathogenesis of ITP prompted the development of therapeutic strategies based on the stimulation of the TPO receptor...
2016: ImmunoTargets and Therapy
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