Fit-for-purpose validation of a drug-tolerant immunogenicity assay for a human mAb drug in animal safety studies.

A modified biotin-drug extraction and acid dissociation (BEAD) immunogenicity assay was developed to detect anti-drug-antibodies (ADA) against the human anti-FXIIa monoclonal antibody (mAb) drug, Garadacimab (previously called CSL312). Multiple strategies were tested to optimize the signal-to-background (S/B) ratio, assay sensitivity and the drug tolerance. The modified BEAD assay was found to be highly drug tolerant (>500 μg/ml) with a sensitivity of 100 ng/ml, in line with current FDA regulatory guidelines.

Airway inflammation and dysbiosis in antibody deficiency despite the presence of IgG.

Background: Patients with antibody deficiency suffer chronic respiratory symptoms, recurrent exacerbations, and progressive airways disease despite systemic replacement of IgG. Little is known about the respiratory tract biology of these patients.

Objective: We sought to measure immunoglobulin levels, inflammatory cytokines, and mediators of tissue damage in serum and sputum from patients with antibody deficiency and healthy controls; to analyze the respiratory microbiome in the same cohorts.

Comparative Transcriptomic Analysis of Temozolomide Resistant Primary GBM Stem-Like Cells and Recurrent GBM Identifies Up-Regulation of the Carbonic Anhydrase Gene as Resistance Factor.

About 95% of patients with Glioblastoma (GBM) show tumor relapse, leaving them with limited therapeutic options as recurrent tumors are most often resistant to the first line chemotherapy standard Temozolomide (TMZ). To identify molecular pathways involved in TMZ resistance, primary GBM Stem-like Cells (GSCs) were isolated, characterized, and selected for TMZ resistance in vitro. Subsequently, RNA sequencing analysis was performed and revealed a total of 49 differentially expressed genes (|log2-fold change| > 0.

Interaction of Discoidin Domain Receptor 1 with a 14-3-3-Beclin-1-Akt1 Complex Modulates Glioblastoma Therapy Sensitivity.

Glioblastoma (GBM) is highly refractory to therapy and associated with poor clinical outcome. Here, we reveal a critical function of the promitotic and adhesion-mediating discoidin domain receptor 1 (DDR1) in modulating GBM therapy resistance. In GBM cultures and clinical samples, we show a DDR1 and GBM stem cell marker co-expression that correlates with patient outcome.

A Rationale for Targeting Extracellular Regulated Kinases ERK1 and ERK2 in Glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain tumor. It still carries a grim prognosis and new therapies are needed. This review summarizes the current status of mechanistic insights into the function of extracellular regulated kinase (ERK) and its potential as a therapeutic target for patients with GBM.