A5081181816- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Immunodeficiency and Autoimmune Disorders
- Renal Transplantation Outcomes and Treatments
- Complement system in diseases
- Immune Cell Function and Interaction
- Toxin Mechanisms and Immunotoxins
- Immunotherapy and Immune Responses
- Pneumocystis jirovecii pneumonia detection and treatment
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Renal Diseases and Glomerulopathies
- Asthma and respiratory diseases
- Pharmacological Effects and Toxicity Studies
- Dialysis and Renal Disease Management
- Autoimmune Bullous Skin Diseases
- Pancreatic function and diabetes
- Herpesvirus Infections and Treatments
- Respiratory and Cough-Related Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cystic Fibrosis Research Advances
- Urticaria and Related Conditions
- Transgenic Plants and Applications
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
Hansa Biopharma (Sweden)
2015-2025
Active Biotech (Sweden)
2001-2006
AstraZeneca (Sweden)
1999-2000
IdeS is a streptococcal protease that cleaves IgG antibodies into F(ab’)2 and Fc fragments with unique degree of specificity, thereby providing novel treatment opportunity IgG-driven autoimmune conditions antibody mediated transplant rejection. Here we report the results from first in man, double blinded randomized study single ascending doses healthy, male subjects. Twenty healthy subjects were given intravenous IdeS. With impressive efficacy cleaved entire plasma IgG-pool only minutes...
Background. Highly HLA sensitized patients have limited access to life-saving kidney transplantation because of a paucity immunologically suitable donors. Imlifidase is cysteine protease that cleaves IgG leading rapid decrease in antibody level and inhibition IgG-mediated injury. This study investigates the efficacy safety imlifidase converting positive crossmatch test negative, allowing highly be transplanted with living or deceased donor kidney. Methods. open-label, single-arm, phase 2...
Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. converts positive crossmatch to potential donor (T cell, B or both), negative, enabling transplantation occur between previously HLA incompatible donor-recipient pairs. To date, 39 patients received imlifidase prior kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for who were AMR+ compared AMR-, death-censored allograft...
Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds tested in mice their inhibitory effects on disease development the acute experimental encephalomyelitis model selected beagle dog induction proinflammatory reaction. Structure−activity relationships are discussed. Compound 8c, laquinimod, showed improved potency superior toxicological profile compared to lead compound roquinimex (1b, Linomide) was clinical...
Antibody-mediated rejection (ABMR) poses a barrier to long-term graft survival and is one of the most challenging events after kidney transplantation. Removing donor specific antibodies (DSA) through therapeutic plasma exchange (PLEX) cornerstone antibody depletion but has inconsistent effects. Imlifidase treatment currently utilized for desensitization with near-complete inactivation DSA both in intra- extravascular space.
Ag binding to the BCR is a critical step in B cell development and activation, initiating cascade of signaling events ultimately leading proliferation, differentiation, or death. A bacterial enzyme, IgG-degrading enzyme Streptococcus pyogenes (IdeS), was shown specifically cleave IgG molecules below hinge region soluble when bound Ag, resulting one F(ab')2 molecule homodimeric Fc fragment. Whether IdeS could also it present attached membrane complex with CD79a CD79b unknown. In this article,...
Imlifidase is an IgG-cleaving endopeptidase conditionally approved in Europe for desensitization of highly sensitized patients before kidney transplantation. We present 5-y outcomes and donor-specific antibody (DSA) levels clinical trial participants from a single site who received imlifidase incompatible transplantation (NCT02790437). was administered up to 24 h living or deceased donor DSAs were monitored transplantation, at days 7 28, 5 y posttransplant. At y, 8 alive. One these had...
We addressed the question of whether prolonged local retention glucocorticoid (GC) budesonide (BUD) within airway tissue, due to reversible fatty acid esterification, is associated with protracted topical anti-inflammatory activity and improved selectivity, when compared fluticasone propionate (FP). BUD or FP at 25 nmol/kg was administered intratracheally subcutaneously adrenalectomized rats, followed by lipopolysaccharide (LPS) intratracheal instillation. The trachea main bronchi were...
Imlifidase is an immunoglobulin G (IgG)-specific protease conditionally approved in the EU for desensitization highly sensitized crossmatch positive kidney transplant patients. efficiently cleaves both heavy chains of IgG a 2-step process. However, low levels intermediate cleavage product, single-cleaved (scIgG), may persist circulation. The study objective was to investigate Fc-mediated effector functions scIgG and its potential impact on common clinical immunologic assays used assess...
Abstract Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation cellular antibody receptors by endogenous limits antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADCP). Here, we show how enzymatic cleavage using bacterial enzyme IdeS can be utilized to empty both high low affinity Fcγ-receptors clear entire pool. Using in vitro models, tumor animal models as well ex vivo analysis sera collected...
The normal rise of circulating endogenous glucocorticosteroids (GCS), in response to immunological stimuli, can be impaired patients with inflammatory diseases. aim this study was investigate whether abolition the GCS promotes local production pro-inflammatory cytokine, tumour necrosis factor (TNF)-alpha, challenged airways and affects cellular rats. In adrenalectomized or sham operated rats, trachea main bronchi were lavaged at various times after intratracheal instillation low dose...
The aim of this study was to investigate if human IgM is a cleavable substrate for imlifidase and explain an observed effect in anti-HLA single antigen bead (SAB) assays sensitized patients. Serum samples collected pre- 24 h post-imlifidase administration from patients enrolled phase II trial were investigated IgG using SAB assays, with without vitro depletion CaptureSelect™ affinity matrix. In addition, pre-dose purified treated evaluated by SDS-PAGE, Western blot (PE-conjugated anti-human...
<div>Abstract<p>Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation cellular antibody receptors by endogenous limits antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADCP). Here, we show how enzymatic cleavage using bacterial enzyme IdeS can be utilized to empty both high low affinity Fcγ-receptors clear entire pool. Using <i>in vitro</i> models, tumor animal models...
<div>Abstract<p>Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation cellular antibody receptors by endogenous limits antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADCP). Here, we show how enzymatic cleavage using bacterial enzyme IdeS can be utilized to empty both high low affinity Fcγ-receptors clear entire pool. Using <i>in vitro</i> models, tumor animal models...
<p>IdeS effect on Daudi cell proliferation for 48 hours</p>
<p>SDS-PAGE separation of plasma treated with 10 ÂÃ,âµg/mL IdeS</p>
<p>Human IgG concentration in mouse serum after a single i.p. administration of 1 g/kg IVIg SCID mice.</p>
<p>SDS-PAGE separation of plasma treated with 10 ÂÃ,âµg/mL IdeS</p>
<p>Human IgG concentration in mouse serum after a single i.p. administration of 1 g/kg IVIg SCID mice.</p>