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Revista de Neurologia Apr 2018
Topics: Daclizumab; Humans; Immunosuppressive Agents; Interferon-beta; Multiple Sclerosis
PubMed: 29645067
DOI: No ID Found -
Ophthalmology and Therapy Dec 2021Scleritis refers to a wide spectrum of ocular conditions ranging from mild to sight-threatening scleral inflammation that may compromise visual function and threaten the... (Review)
Review
Scleritis refers to a wide spectrum of ocular conditions ranging from mild to sight-threatening scleral inflammation that may compromise visual function and threaten the anatomical integrity of the ocular globe. Most aggressive forms like necrotizing or posterior scleritis are often difficult-to-treat cases, refractory to conventional treatment. The association with systemic diseases, namely rheumatoid arthritis, Sjögren syndrome, granulomatosis with polyangiitis, and relapsing polychondritis, may have prognostic implications as well. A better understanding of the pathogenesis of ocular inflammatory diseases have paved the way to more effective and targeted treatment approaches. In this regard, a growing body of evidence supports the potential role of biologic agents in the management of non-infectious scleral inflammation, either idiopathic or in a background of immune-mediated systemic disorders. Biologic agents such as anti-tumor necrosis factor agents, interleukin-1 and interleukin-6 inhibitors as well as CD20 blockade have displayed promising results. More specifically, several studies have reported their ability to control scleral inflammation, reduce the overall scleritis relapses, and allow a glucocorticoid-sparing effect while being generally well tolerated. Anecdotal reports have also been described with other biologic agents including abatacept, ustekinumab, daclizumab, and alemtuzumab as well as targeted small molecules such as tofacitinib. Further studies are warranted to fully elucidate the role of biologic agents in non-infectious scleritis and investigate specific areas with the aim to administer treatments in the context of personalized medicine. This review summarizes the available data regarding clinical trials, small pilot studies, and real-life experience of the last two decades reporting the use of biologic agents in the management of non-infectious scleritis.
PubMed: 34476773
DOI: 10.1007/s40123-021-00393-8 -
Archivum Immunologiae Et Therapiae... 2006Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been... (Review)
Review
Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been implicated in many human cancers and is associated with poor prognosis. Tumor growth has been shown to be decreased by interrupting this process of extensive growth factor-mediated signaling by directly targeting either the surface receptor or the ligand and thereby preventing cell survival and promoting apoptosis. Monoclonal antibodies have long been eyed as a potential new class of therapeutics targeting cancer and other diseases. Antibody-based therapy initially entered clinical practice when trastuzumab/Herceptin became the first clinically approved drug against an oncogene product as a well-established blocking reagent for tumors with hyperactivity of epidermal growth factor signaling pathways. In the first part of this review we explain basic terms related to the development of antibody-based drugs, give a brief historic perspective of the field, and also touch on topics such as the "humanization of antibodie" or creation of hybrid antibodies. The second part of the review gives an overview of the clinical usage of bispecific antibodies and antibodies "armed" with cytotoxic agents or enzymes. Further within this section, cancer-specific, site-specific, or signaling pathway-specific therapies are discussed in detail. Among other antibody-based therapeutic products, we discuss: Avastin (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX-210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000), Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of the review deliberates upon potential problems associated with cancer immunotherapy.
Topics: Antibodies, Bispecific; Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Agents; Drug Design; Humans; Neoplasms; Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Tumor Necrosis Factor; Signal Transduction
PubMed: 16648969
DOI: 10.1007/s00005-006-0011-5 -
Bone Marrow Transplantation Mar 2011Treatment options for steroid-refractory GVHD (SR-GVHD) are unsatisfactory and prognosis is poor. Inflammatory cytokines IL-2 and TNF-α are important mediators of GVHD...
Treatment options for steroid-refractory GVHD (SR-GVHD) are unsatisfactory and prognosis is poor. Inflammatory cytokines IL-2 and TNF-α are important mediators of GVHD and may be critical targets for therapy. We retrospectively reviewed our experience using combination anti-cytokine therapy of daclizumab and infliximab. Seventeen evaluable patients had a median age of 47 years (range 35-63). The conditioning regimen was myeloablative in 13 and non-myeloablative in 4 cases. GVHD occurred at a median of 49 days after transplant in 12 patients (range 21-231 days) and at a median of 46 days (range 25-119 days) after donor lymphocyte infusion in 5 patients. All patients had persistent or progressive GVHD despite 1-2 mg/kg/day of corticosteroids for a median of 7 days (range 2-26 days). They received a combination of daclizumab and infliximab for acute GVHD IBMTR severity index B (3), C (10) or D (4). Of the 17 patients analyzed, 47% responded to treatment, 24% had complete resolution of symptoms and 24% had partial responses. Survival was limited and all the patients died a median of 6.7 months (range 1.6-26) from transplant and 35 days from initiation of daclizumab/infliximab. This retrospective analysis suggests that combination anti-cytokine therapy with daclizumab/infliximab has significant activity in SR-GVHD, but outcomes remain poor. New methods to prevent and treat GVHD are urgently needed.
Topics: Acute Disease; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Drug Resistance; Female; Graft vs Host Disease; Humans; Immunoglobulin G; Immunosuppressive Agents; Infliximab; Male; Middle Aged; Prognosis; Retrospective Studies; Steroids; Survival Analysis; Treatment Outcome
PubMed: 20498647
DOI: 10.1038/bmt.2010.117 -
Biomedicines Mar 2019Daclizumab (DAC) is a humanized, monoclonal antibody that blocks CD25, a critical element of the high-affinity interleukin-2 receptor (IL-2R). DAC HYP blockade of CD25... (Review)
Review
Daclizumab: Mechanisms of Action, Therapeutic Efficacy, Adverse Events and Its Uncovering the Potential Role of Innate Immune System Recruitment as a Treatment Strategy for Relapsing Multiple Sclerosis.
Daclizumab (DAC) is a humanized, monoclonal antibody that blocks CD25, a critical element of the high-affinity interleukin-2 receptor (IL-2R). DAC HYP blockade of CD25 inhibits effector T cell activation, regulatory T cell expansion and survival, and activation-induced T-cell apoptosis. Because CD25 blockade reduces IL-2 consumption by effector T cells, it increases IL-2 bioavailability allowing for greater interaction with the intermediate-affinity IL-2R, and therefore drives the expansion of CD56 natural killer (NK) cells. Furthermore, there appears to be a direct correlation between CD56 NK cell expansion and DAC HYP efficacy in reducing relapses and MRI evidence of disease activity in patients with RMS in phase II and phase III double-blind, placebo- and active comparator-controlled trials. Therapeutic efficacy was maintained during open-label extension studies. However, treatment was associated with an increased risk of rare adverse events, including cutaneous inflammation, autoimmune hepatitis, central nervous system Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) syndrome, and autoimmune Glial Fibrillary Acidic Protein (GFAP) alpha immunoglobulin-associated encephalitis. As a result, DAC HYP was removed from clinical use in 2018. The lingering importance of DAC is that its use led to a deeper understanding of the underappreciated role of innate immunity in the potential treatment of autoimmune disease.
PubMed: 30862055
DOI: 10.3390/biomedicines7010018 -
British Journal of Pharmacology Jun 2012Monoclonal antibodies (mAbs) and fusion proteins directed towards cell surface targets make an important contribution to the treatment of disease. The purpose of this... (Review)
Review
Monoclonal antibodies (mAbs) and fusion proteins directed towards cell surface targets make an important contribution to the treatment of disease. The purpose of this review was to correlate the clinical and preclinical data on the 15 currently approved mAbs and fusion proteins targeted to the cell surface. The principal sources used to gather data were: the peer reviewed Literature; European Medicines Agency 'Scientific Discussions'; and the US Food and Drug Administration 'Pharmacology/Toxicology Reviews' and package inserts (United States Prescribing Information). Data on the 15 approved biopharmaceuticals were included: abatacept; abciximab; alefacept; alemtuzumab; basiliximab; cetuximab; daclizumab; efalizumab; ipilimumab; muromonab; natalizumab; panitumumab; rituximab; tocilizumab; and trastuzumab. For statistical analysis of concordance, data from these 15 were combined with data on the approved mAbs and fusion proteins directed towards soluble targets. Good concordance with human pharmacodynamics was found for mice receiving surrogates or non-human primates (NHPs) receiving the human pharmaceutical. In contrast, there was poor concordance for human pharmacodynamics in genetically deficient mice and for human adverse effects in all three test systems. No evidence that NHPs have superior predictive value was found.
Topics: Animals; Antibodies, Monoclonal; Drug Evaluation, Preclinical; Humans; Maximum Tolerated Dose; No-Observed-Adverse-Effect Level; Pharmacology, Clinical; Predictive Value of Tests; Receptors, Cell Surface; Recombinant Fusion Proteins; Solubility; Species Specificity
PubMed: 22168282
DOI: 10.1111/j.1476-5381.2011.01811.x -
Biologics : Targets & Therapy 2016Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with... (Review)
Review
Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit-risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56(bright) natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies.
PubMed: 27672308
DOI: 10.2147/BTT.S89218 -
EBioMedicine Feb 2017Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal... (Review)
Review
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells. This depletion was substantial and long-term following CD52 and CD20-depletion, and both also induced long-term inhibition of MS with few treatment cycles, indicating induction-therapy activity. Importantly, memory B cells were augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that are known to worsen MS. This creates a unifying concept centered on memory B cells that is consistent with therapeutic, histopathological and etiological aspects of MS.
Topics: B-Lymphocytes; Cytokines; Humans; Immunologic Memory; Immunotherapy; Inflammation Mediators; Models, Immunological; Molecular Targeted Therapy; Multiple Sclerosis, Relapsing-Remitting; Plasma Cells
PubMed: 28161400
DOI: 10.1016/j.ebiom.2017.01.042 -
Autoimmune Diseases 2019Monoclonal antibodies constitute a potent and broadly tolerable drug class, representing for some conditions the first newly approved treatment in years. As such, many... (Review)
Review
BACKGROUND
Monoclonal antibodies constitute a potent and broadly tolerable drug class, representing for some conditions the first newly approved treatment in years. As such, many are afforded "fast-track" or "breakthrough therapy" designations by the U.S. Food and Drug Administration, leading to provisional approval before Phase III clinical trials are reported. Although these drugs are usually safe, some patients experience life-threatening complications-myositis and encephalitis have led to permanent or temporary recalls. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity condition easily missed due to its long incubation period and nonspecific presentation. This minireview is primarily intended as an abbreviated guide for practitioners who may be using these powerful treatments.
METHODOLOGY
We searched PubMed using a string of symptoms consistent with DRESS syndrome and monoclonal antibodies approved by the FDA since 2015. Then, we excluded studies reporting dermatological complications of reactivation of nonherpetic infection, immunodeficiency-related infection, or reactions to the injection site or infusion. We searched for and accessed prior reviews and background studies via PubMed, Mendeley, and Google Scholar.
RESULTS
Two cases of DRESS syndrome were identified in the literature, both the result of treatment with daclizumab. There was one additional case of encephalitis without cutaneous symptoms caused by daclizumab. Drug-induced hypersensitivity dermatitis was reported following treatment with nivolumab and two cases of combination treatment with ipilimumab and either nivolumab or durvalumab produced maculopapular rash and bullae in the first patient and lichenoid dermatitis and blisters in the second patient.
CONCLUSIONS
Daclizumab was the only recently approved monoclonal antibody associated with DRESS syndrome as such. Limitations in the diagnostic reliability of DRESS syndrome as a clinical entity and the lack of negative clinical trial reporting suggest enhanced vigilance on the part of clinicians and regulators may be warranted.
PubMed: 31308976
DOI: 10.1155/2019/7595706