Managing the Impact of Immunogenicity in an Era of Immunotherapy: From Bench to Bedside.

Biotherapeutics have revolutionized our ability to treat life-threatening diseases. Despite clinical success, the use of biotherapeutics has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs). The multifactorial nature of immunogenicity has prevented a standardized approach for assessing this and each of the assessment methods developed so far does not exhibit high enough reliability to be used alone, due to limited predictiveness.

Enabling Routine MHC-II-Associated Peptide Proteomics for Risk Assessment of Drug-Induced Immunogenicity.

Major histocompatibility complex-II (MHC-II)-Associated Peptide Proteomics (MAPPs) is a mass spectrometry-based approach to identify and relatively quantitate naturally processed and presented MHC-II-associated peptides that can potentially activate T cells and contribute to the immunogenicity of a drug. Acceptance of the MAPPs technology as an appropriate preclinical (and potentially clinical) immunogenicity risk assessment tool depends not only on its technical stability and robustness but also on the ability to compare results across experiments and donors. To this end, we developed a specialized MAPPs data processing pipeline, dataMAPPs, which presents complex mass spectrometric data sets in the form of heat maps (heatMAPPs), enabling rapid and convenient comparison between conditions and donors.

Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker.

Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of progression while in early stages of CKD. To address this challenge, a renal biopsy transcriptome-driven approach was applied to develop noninvasive prognostic biomarkers for CKD progression.

First-in-Man Study With Inclacumab, a Human Monoclonal Antibody Against P-selectin.

Inclacumab, a novel monoclonal antibody against P-selectin in development for the treatment and prevention of atherosclerotic cardiovascular diseases, was administered in an ascending single-dose study as intravenous infusion to evaluate safety, pharmacokinetics, and pharmacodynamics. Fifty-six healthy subjects were enrolled in this randomized, double-blind placebo-controlled study. Each dose level (0.

Cardiovascular risk markers associated with arterial calcification in patients with chronic kidney disease Stages 3 and 4.

Background: The contribution of pro-inflammatory markers to cardiovascular (CV) risk and vascular calcification in chronic kidney disease (CKD) remains largely to be elucidated. We investigated the association between plasma levels of several biomarkers and calcification volume in three different vascular beds in CKD Stages 3 and 4 patients.

Methods: This is a cross-sectional, exploratory study in patients with an estimated glomerular filtration rate (eGFR) ≥20 and ≤45 mL/min/1.

Antibody-based proteomics and biomarker research - current status and limitations.

Antibody-based proteomics play a very important role in biomarker discovery and validation, facilitating the high-throughput evaluation of candidate markers. Most proteomics-driven discovery is nowadays based on the use of MS. MS has many advantages, including its suitability for hypothesis-free biomarker discovery, since information on protein content of a sample is not required prior to analysis.

HLA-G, pre-eclampsia, immunity and vascular events.

Pre-eclampsia, one of the main complications in pregnancy, is characterised by shallow cytotrophoblast invasion of decidua as well as by vascular endothelial cell dysfunction, leading to a poor perfusion of placenta. A striking feature of pre-eclamptic pregnancies is that expression of HLA-G protein is reduced in term placentas compared with normal pregnancy. How such HLA-G deficient expression may be related to the pre-eclamptic pathology is unknown.

Secretion of pro-apoptotic intron 4-retaining soluble HLA-G1 by human villous trophoblast.

One major materno-fetal interface in the human placenta is constituted by the syncytiotrophoblast, in contact with maternal blood of the intervillous space, which derives from differentiation and fusion of the villous cytotrophoblast (vct). In the present work, we purified vct from term placenta by depleting HLA class I- and class II-positive cells. We found by RT-PCR that both soluble intron 4-retaining HLA-G1 (sHLA-G1) and HLA-G2 isoforms were transcribed in purified vct.