Implementation of a Three-Way Comparability Assessment for a Bioanalytical Anti-Drug Antibody Method.

Immunogenicity evaluation is a critical part of drug development. Regulatory guidelines from multiple health agencies provide recommendations for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity in clinical trials. These recommendations primarily describe an ADA method run in one bioanalytical laboratory supporting a biotherapeutic molecule; however, there are increasing instances that may necessitate the support of the ADA method being run in more than one laboratory.

A Fit-for-Purpose Method to Measure Circulating Levels of the mRNA Component of a Liposomal-Formulated Individualized Neoantigen-Specific Therapy for Cancer.

Autogene cevumeran is an individualized neoantigen-specific therapy (iNeST) under development for the treatment of various solid tumors. It consists of an RNA-Lipoplex (RNA-LPX) in which the encapsulated mRNA molecule encodes up to ten neoepitopes identified from each individual patient. In association with major histocompatibility complex (MHC) class I and MHC class II, these neoantigens can potentially stimulate and expand neoantigen-specific CD4+ and CD8+ T cells, leading to antitumor responses.

Chronic illness in childhood and early adolescence: A longitudinal exploration of co-occurring mental illness.

Chronic health conditions are hypothesized to disrupt the typical trajectory of child and adolescent development, and subsequently lead to increased levels of mental illness. However, due to methodological limitations in existing studies, this theory remains to be fully substantiated by empirical research. This study aimed to more thoroughly test hypotheses in the field.

Low-Grade Appendiceal Mucinous Neoplasm in an Adolescent Patient With Untreated Crohn's Disease.

Appendiceal mucinous neoplasms are rarely diagnosed in pediatric patients. We present a 16-year-old adolescent boy with severe Crohn's disease who was not on maintenance medication for his underlying diagnosis. He was referred for nutritional optimization and small bowel obstruction.

Psychiatric outcomes associated with chronic illness in adolescence: A systematic review.

Recent years have seen an increased focus on the high rates of psychiatric comorbidities in adults with chronic illness. This systematic review explored whether chronic illness in adolescents was similarly associated with poor psychiatric outcomes. The literature search identified 129 articles, only 5 of which were indicated to be at a low risk of methodological bias.

Bioanalytical qualification of clinical biomarker assays in plasma using a novel multi-analyte Simple Plex platform.

Aim: Immune-checkpoint inhibitors are presumed to break down the tolerogenic state of immune cells by activating T-lymphocytes that release cytokines and enhance effector cell function for elimination of tumors. Measurement of cytokines is being pursued for better understanding of the mechanism of action of immune-checkpoint inhibitors, as well as to identify potential predictive biomarkers.

Results: In this study, we show bioanalytical qualification of cytokine assays in plasma on a novel multi-analyte immunoassay platform, Simple Plex.

Preexisting Antibodies to an F(ab')2 Antibody Therapeutic and Novel Method for Immunogenicity Assessment.

Anti-therapeutic antibodies (ATAs) may impact drug exposure and activity and induce immune complex mediated toxicity; therefore the accurate measurement of ATA is important for the analysis of drug safety and efficacy. Preexisting ATAs to the hinge region of anti-Delta like ligand 4 (anti-DLL4) F(ab')2, a potential antitumor therapeutic, were detected in cynomolgus monkey serum, which presented a challenge in developing assays for detecting treatment induced ATA. A total ATA assay was developed using a bridging ELISA that detected both anti-CDR and anti-framework ATA including anti-hinge reactivity.

Preclinical pharmacokinetics of MFGR1877A, a human monoclonal antibody to FGFR3, and prediction of its efficacious clinical dose for the treatment of t(4;14)-positive multiple myeloma.

Purpose: MFGR1877A is a human IgG1 monoclonal antibody that binds to fibroblast growth factor receptor 3 (FGFR3) and is being investigated as a potential therapy for relapsed/refractory FGFR3+ multiple myeloma. The purpose of these studies was to characterize the pharmacokinetics (PK) of MFGR1877A in mouse, rat, and monkey and predict its human PK and efficacious dose.

Methods: PK of MFGR1877A was determined in athymic nude mice, Sprague-Dawley rats and cynomolgus monkeys after administration of single intravenous doses.

Quest for a realistic in vivo test method for antimicrobial hand-rub agents: introduction of a low-volume hand contamination procedure.

A novel method has been developed for the evaluation of alcohol-based hand rubs (ABHR) that employs a hand contamination procedure that more closely simulates the in-use conditions of ABHR. Hands of human subjects were contaminated with 0.2 ml of a concentrated suspension of Serratia marcescens (ATCC 14756) to achieve baseline contamination between 8 and 9 log₁₀ CFU/hand while allowing product to be applied to dry hands with minimal soil load.

Association of endogenous anti-interferon-α autoantibodies with decreased interferon-pathway and disease activity in patients with systemic lupus erythematosus.

Objective: Numerous observations implicate interferon-α (IFNα) in the pathophysiology of systemic lupus erythematosus (SLE); however, the potential impact of endogenous anti-IFNα autoantibodies (AIAAs) on IFN-pathway and disease activity is unclear. The aim of this study was to characterize IFN-pathway activity and the serologic and clinical profiles of AIAA-positive patients with SLE.

Methods: Sera obtained from patients with SLE (n = 49), patients with rheumatoid arthritis (n = 25), and healthy control subjects (n = 25) were examined for the presence of AIAAs, using a biosensor immunoassay.

Ethanol stimulates tumor progression and expression of vascular endothelial growth factor in chick embryos.

Background: The mechanisms by which alcohol consumption causes cancer have not been established due to a lack of experimental studies.

Methods: A chick embryo chorioallantoic membrane (CAM) model that bore human fibrosarcoma (HT1080) was used to determine whether the administration of physiologically relevant doses of ethanol could stimulate tumor growth, angiogenesis, metastasis, and vascular endothelial growth factor (VEGF) expression in tumors. HT1080 cells were inoculated onto the "upper CAM" on Day 8, saline or ethanol was administrated at a dose of 0.

A clinical study comparing the skin antisepsis and safety of ChloraPrep, 70% isopropyl alcohol, and 2% aqueous chlorhexidine.

ChloraPrep (2% chlorhexidine gluconate + 70% isopropyl alcohol [CHG + IPA] in a 3.0-mL applicator) is a recently approved antiseptic for preoperative skin preparation. This controlled open-label trial assessed the immediate and persistent antimicrobial efficacy and safety of CHG + IPA compared with 70% IPA or a 2% CHG aqueous solution alone.