IgA nephropathy is the most common primary glomerulonephritis worldwide and carries a substantial risk of kidney failure. New agency-approved therapies, either specifically for or chronic disease in general, hold out hope mitigating renal deterioration patients with nephropathy. The latest addition to this therapeutic armamentarium targets endothelin-A receptor (ETAR). Activation ETAR on multip...

Abstract Biologics targeting multiple pathways and/or cell types simultaneously have the potential to restore normal immune homeostasis. Inhibitory checkpoint receptor agonism by antibodies benefits from higher order clustering for strong activation, which can be achieved antibody Fc binding gamma receptors (FcγRs). However, many of current agonist non discriminately bind activating FcγRs. This...

mammalian expression systems, due to their capacity in post-translational modification, are preferred systems for biopharmaceutical protein production. several recombinant protein systems have been introduced to the market, most of which are under clinical development. in spite of significant improvements such as cell line engineering, introducing novel expression methods, gene silencing and pr...

Multi-target-directed ligands (MTDLs) offer new hope for the treatment of multifactorial complex diseases such as Alzheimer's Disease (AD). Herein, we present compounds aimed at targeting the NMDA and the P2X7 receptors, which embody a different approach to AD therapy. On one hand, we are seeking to delay neurodegeneration targeting the glutamatergic NMDA receptors; on the other hand, we also a...

Objectives Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and local inflammation, which are regulated the immune system. The immunological aspects of this unclear. Immunoglobulin A regulates many cell responses through interactions with Fcα receptor type I (FcαRI). Anti-FcαRI antibody inhibits activating receptors inducing an inhibitory immunoreceptor tyro...

Spacer or co-stimulatory components in chimeric antigen receptor (CAR) design influence CAR T cell effector function. Few preclinical mouse models optimally support candidate pre-selection for clinical development. Here we use a model which murine cells can be exploited with human tumor xenografts. This mouse-in-mouse approach avoids limitations caused by species-specific factors crucial surviv...

Antigen (Ag) targeting is an efficient way to induce immune responses. Ag is usually coupled to an antibody (Ab) specific for a receptor expressed on dendritic cells (DCs), and then the Ag-anti-receptor is inoculated with an adjuvant. Here we report that targeting Ag to a receptor expressed on both B cells and DCs, the TLR orphan receptor CD180, in the absence of adjuvant rapidly induced IgG re...

As an alternative therapeutic treatment to reduce or eliminate the current side effects associated with advanced prostate cancer (PCa) chemotherapy, a multifunctional double-receptor-targeting iron oxide nanoparticles (IONPs) (luteinizing hormone-releasing hormone receptor [LHRH-R] peptide- and urokinase-type plasminogen activator receptor [uPAR] peptide-targeted iron oxide nanoparticles, LHRH-...

Endocrine therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%-30% of cases that are ER negative (ER-). Androgen receptor (AR) is expressed in 60%-70% of breast tumors, independent of ER status. How androgens and AR regulate breast cancer growth remains largely unknown. We find that AR is enriched in ER- breast tumors that overexpress HER2. Through analy...