Human antibody

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker. PATIENTS AND METHODS: TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors...

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels...

BACKGROUND Scleroderma is a chronic autoimmune disease characterized by angiopathy, autoimmunity, and fibrosis. One form of scleroderma, systemic sclerosis, is characterized by diffuse skin lesions and visceral involvement. Eosinophilic pleural effusion is a rare complication attributed to a large array of diseases. We present a case of a man with underlying systemic sclerosis who developed eosinophilic pleural effusion as a complication of associated Trichinella spiralis infection. CASE REPORT A 49-year-old man presented for bilateral inflammatory radio-ulnar-carpal joint pain, paresthesia of the hands and forearms and a 2-week history of right posterior aching thoracic pain and night sweats...

PURPOSE: Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs). METHODS: We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes...

MOTIVATION: Antibody therapeutic candidates must exhibit not only tight binding to their target but also good developability properties, especially low risk of immunogenicity. RESULTS: In this work, we fit a simple generative model, SAM, to sixty million human heavy and seventy million human light chains. We show that the probability of a sequence calculated by the model distinguishes human sequences from other species with the same or better accuracy on a variety of benchmark datasets containing >400 million sequences than any other model in the literature, outperforming large language models (LLMs) by large margins...

BACKGROUND AIMS: HCV infection continues to be a major global health burden, despite effective antiviral treatments. The urgent need for a protective vaccine is hindered by the scarcity of suitable HCV permissive animal models tractable in vaccination and challenge studies. Currently, only antibody neutralization studies in infectious cell culture systems or studies of protection by passive immunization of human-liver chimeric mice offer the possibility to evaluate the effect of vaccine-induced antibodies...

Peptide mapping with mass spectrometry (MS) is an important tool for protein characterization in the biopharmaceutical industry. Historically, peptide mapping monitors post-translational modifications (PTMs) of protein products and process intermediates during development. Multi-attribute monitoring (MAM) methods have been used previously in commercial release and stability testing panels to ensure control of selected critical quality attributes (CQAs). Our goal is to use MAM methods as part of an overall analytical testing strategy specifically focused on CQAs, while removing or replacing historical separation methods that do not effectively distinguish CQAs from non-CQAs due to co-elution...

IMPORTANCE: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. OBJECTIVE: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France...

Enzyme-linked immunosorbent assay (ELISA) is the gold standard technique for measuring protein biomarkers due to its high sensitivity, specificity, and throughput. Despite its success, continuous advancements in ELISA and immunoassay formats are crucial to meet evolving global challenges and to address new analytical needs in diverse applications. To expand the capabilities and applications of immunoassays, we introduce a novel ELISA-like assay that we call Bioluminescent-bacteria-linked immunosorbent assay (BBLISA)...

Dear Editor, Ticks carry many diseases, bacteria, and viruses and represent a very important healthcare issue both in Croatia and globally. Although most ticks are not infected with pathogens dangerous to humans, some ticks can transmit infectious diseases with significant morbidity and mortality. This is caused by the increasing incidence of many tick-borne diseases over a growing geographical area. Many factors influence which species of ticks are present in a given geographical area, as well as the density of their population and the risk of human exposure to infected ticks...

Background: Hepatitis E virus (HEV) is transmitted by the fecal route, usually through contaminated water in humans and/or infected animals, especially pigs. The objective of this study was to evaluate the level of anti-HEV antibodies in a panel of pig sera and to identify HEV in pig feces in farms. Methodology: The presence of HEV antibodies was tested by an in-house ELISA and a commercial ELISA IDvet. HEV genome was assessed by nested RT-PCR, and then, genotype was identified by sequencing (MinION Nanopore technology)...

The activation of CD40-mediated signaling in antigen-presenting cells is a promising therapeutic strategy to promote immune responses against tumors. Most agonistic anti-CD40 antibodies currently in development require the Fcγ-receptor (FcγR)-mediated crosslinking of CD40 molecules for a meaningful activation of CD40 signaling but have limitations due to dose-limiting toxicities. Here we describe the identification of CD40 antibodies which strongly stimulate antigen-presenting cells in an entirely FcγR-independent manner...

Aflibercept is a therapeutic recombinant fusion protein comprising extracellular domains of human vascular endothelial growth factor receptors (VEGFRs) and IgG1-Fc. It is a highly glycosylated protein with five N-glycosylation sites that might impact it structurally and/or functionally. Aflibercept is produced in mammalian cells and exhibits large glycan heterogeneity, which hampers glycan-associated investigations. Here, we report the expression of aflibercept in a plant-based system with targeted N-glycosylation profiles...

Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells to promote T1D pathogenesis. Disrupting B cell APC function prevents T1D in mouse models and has shown promise in clinical trials. Autoantigen-specific B cells thus hold potential as sophisticated T1D biomarkers and therapeutic targets...

Chinese hamster ovary (CHO) cells are the commonly used mammalian host system to manufacture recombinant proteins including monoclonal antibodies. However unfavorable non-human glycoprofile displayed on CHO-produced monoclonal antibodies have negative impacts on product quality, pharmacokinetics, and therapeutic efficiency. Glycoengineering such as genetic elimination of genes involved in glycosylation pathway in CHO cells is a viable solution but constrained due to longer timeline and laborious workflow. Here, in this proof-of-concept (PoC) study, we present a novel approach coined CellEDIT to engineer CHO cells by intranuclear delivery of the CRISPR components to single cells using the FluidFM technology...

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10 mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1...

BACKGROUND: Retifanlimab is a humanized monoclonal antibody targeting programmed death protein-1, and INCB001158 is an oral arginase inhibitor. This phase Ib study investigated retifanlimab, INCB001158, and their combination in Japanese patients with advanced solid tumors. METHODS: Patients received retifanlimab (500 mg every 4 weeks [Q4W] i.v.) or escalating doses of INCB001158 (75 or 100 mg twice daily [BID]) monotherapy in Part 1 and combination of retifanlimab (500 mg Q4W) and INCB001158 (100 mg BID) in Part 2...

BACKGROUND: Up to 20% of people with HIV (PWH) fail to recover their CD4+ T cell counts to levels similar to healthy controls after suppressive antiretroviral therapy (ART). Immune non-responders (INRs) are PWH on suppressive ART with CD4+ T cell counts lower than 350 cells/mL, whereas their CD8+ T cell counts are higher than healthy controls. We are the first group to report that increased anti-CD4 autoantibody IgGs in INRs are responsible for blunted CD4+ T cell reconstitution in PWH with ART and viral suppression through anti-CD4 IgG-induced antibody-mediated cytotoxicity (ADCC) against CD4+ T cells in vitro ...

For several years, we have been committed to exploring the potential of Bordetella pertussis -derived outer membrane vesicles (OMV Bp ) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMV Bp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMV Bp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S)...

Arenaviruses belonging to the Arenaviridae family, genus mammarenavirus, are enveloped, single-stranded RNA viruses primarily found in rodent species, that cause severe hemorrhagic fever in humans. With high mortality rates and limited treatment options, the search for effective antivirals is imperative. Current treatments, notably ribavirin and other nucleoside inhibitors, are only partially effective and have significant side effects. The high lethality and lack of treatment, coupled with the absence of vaccines for all but Junín virus, has led to the classification of these viruses as Category A pathogens by the Centers for Disease Control (CDC)...