Search results for "Humanized"
showing 10 items of 324 documents
Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after daclizumab induction and tacrolimus with mycophenolate mofetil in li…
2008
Introduction. Long-term steroid administration may predispose liver transplant recipients to infectious and metabolic complication. Maintaining effective immunoprophylaxis while minimizing the negative consequences of steroid therapy could be a key factor in improving clinical outcomes.Methods. Six hundred two patients were randomized to receive tacrolimus (TAC) immunosuppression with a single-steroid bolus and two doses of daclizumab (DAC) or mycophenolate mofetil (MMF).Results. The incidence of biopsy-proven acute rejection was 19.7% in the TAC/DAC group and 16.2% in the TAC/ MMF group (ns). Three-month patient and graft survival were similar. Steroid use at month-3 was low at 5.5% in the…
Hepatitis Virus Reactivation in Patients with Psoriasis Treated with Secukinumab in a Real-World Setting of Hepatitis B or Hepatitis C Infection
2022
Background and Objective Biologics for psoriasis, especially anti-tumor necrosis factor-alpha therapies, may reactivate hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, as well in inactive carriers or patients with occult infection. However, some biologics, including anti-interleukin-17 therapies such as secukinumab, seem to be less likely to cause hepatitis reactivation. This study assessed the safety of secukinumab treatment in patients with psoriasis with HBV or HBC infection. Methods This was a retrospective cohort study of patients with moderate-to-severe psoriasis treated with secukinumab at seven Italian centers. Patients serologically positive for one or more of the fo…
Intravitreal injection of bevacizumab induces inflammatory alterations in a uveitis experimental model.
2010
PurposeBevacizumab is currently used as an intravitreal agent in the treatment of inflammatory-associated eye diseases. The aim of the current study is to explore the effects of the intravitreal injection of bevacizumab on aqueous humour cytokines and chemokines in an experimental uveitis model.MethodsEndotoxin-induced uveitis was induced in rats by footpad injections. Bevacizumab was administered by intravitreal injection (75 μg in 3–μL samples) and different chemokine and cytokine proteins were quantified in aqueous humor.ResultsIntravitreal administration of bevacizumab led to a several-fold increase of RANTES, MCP-1, and IFN-γ concentrations in aqueous humor of endotoxin-treated rats.Co…
Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells
2013
Abstract IFN-α is an antineoplastic agent in the treatment of several solid and hematologic malignancies that exerts strong immune- and autoimmune-stimulating activity. However, the mechanisms of immune activation by IFN-α remain incompletely understood, particularly with regard to CD4+CD25highFoxp+ regulatory T cells (Treg). Here, we show that IFN-α deactivates the suppressive function of human Treg by downregulating their intracellular cAMP level. IFN-α–mediated Treg inactivation increased CD4+ effector T-cell activation and natural killer cell tumor cytotoxicity. Mechanistically, repression of cAMP in Treg was caused by IFN-α–induced MAP–ERK kinase (MEK)/extracellular signal-regulated ki…
Impact of immunosuppressive drugs on the therapeutic efficacy of ex vivo expanded human regulatory T cells
2015
Immunosuppressive drugs in clinical transplantation are necessary to inhibit the immune response to donor antigens. Although they are effective in controlling acute rejection, they do not prevent long-term transplant loss from chronic rejection. In addition, immunosuppressive drugs have adverse side effects, including increased rate of infections and malignancies. Adoptive cell therapy with human Tregs represents a promising strategy for the induction of transplantation tolerance. Phase I/II clinical trials in transplanted patients are already underway, involving the infusion of Tregs alongside concurrent immunosuppressive drugs. However, it remains to be determined whether the presence of …
Interleukin-17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin-25-Driven In…
2020
Objective To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. Methods Fecal samples from PsA/SpA patients pre- and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti-interleukin-17A monoclonal antibody inhibitor (IL-17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtai…
EORTC-1203-GITCG - the “INNOVATION”-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab pl…
2019
10–20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) was added to neoadjuvant T and CT, a significant increase in histopathological complete response rate was observed in HER2+ breast cancer. This study aims to investigate the added benefit of using both HER2 targeting drugs (T alone or the combination of T + P), in combination with perioperative CT for localized HER2+ GC. This is a prospective, randomized, open-label, phase II trial. HER2 status from patients with resectable GC (UICC TNM7 tumor stage Ib-III) will be centrally determined.…
Exome Analysis Reveals Genomic Markers Associated with Better Efficacy of Nivolumab in Lung Cancer Patients
2019
Abstract Purpose: Immune checkpoint inhibitors revolutionized the treatment of non-small cell lung cancer (NSCLC). However, only one-quarter of patients benefit from these new therapies. PD-L1 assessment and tumor mutational burden (TMB) are available tools to optimize use of checkpoint inhibitors but novel tools are needed. Exome sequencing could generate many variables but their role in identifying predictors of response is unknown. Experimental Design: We performed somatic and constitutional exome analyses for 77 patients with NSCLC treated with nivolumab. We studied: one-tumor-related characteristics: aneuploidy, CNA clonality, mutational signatures, TMB, mutations in WNT, AKT, MAPK, an…
Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis
2021
Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic mod…
Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes.
2018
BACKGROUND: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution…