Natalizumab

Natalizumab is a recombinant humanized monoclonal antibody and a humanized monoclonal antibody inhibitor that selectively targets α4 integrin (CD49d). Natalizumab binds to the α4β1 heterodimer and blocks its interaction with vascular cell adhesion molecule 1. Natalizumab also prevents lymphocytes from entering the central nervous system, thereby preventing acute demyelinating relapses, and is used in the study of relapsing-remitting multiple sclerosis and Crohn’s disease. Natalizumab possesses anti-inflammatory and immunomodulatory activity, inhibiting the adhesion, retention, and transendothelial migration of immune cells, and reducing the infiltration of inflammatory cells into the central nervous system or affected sites. Natalizumab is also being studied for autoimmune or inflammation-related diseases such as B-cell lymphoma and non-infectious uveitis.

α4β1:19.6 nM (KD), α4β1:0.11 ± 0.01 μg/mL (EC50), α4β1/α4β7 - MadCAM-1-Ig:0.35 ± 0.04 nM, α4β1/α4β7 - Fibronectin:0.32 nM, α4β1/α4β7 - VCAM-1-Ig:0.196 nM

Methods: PBMCs from healthy donors (HD) were sorted into CD4+ and CD8+ T cells. The cells were pretreated for 30 minutes with 2 μg/mL natalizumab, left untreated, or treated with isotype-matched IgG4. After seeding the cells onto VCAM-1-coated plates, they were stimulated for 10 minutes. High-content imaging was used to measure cell adhesion, cell area, aspect ratio, pSLP76 intensity, and F-actin intensity.
Results: Natalizumab treatment significantly reduced T-cell adhesion and spreading on VCAM-1 and decreased pSLP76 and F-actin intensity. PCA analysis clearly distinguished treated from untreated samples. [1]
Methods: In vitro, the binding of natalizumab to VLA-4 (α₄β₁ integrin / CD49d) on the surface of lymphocytes was assessed; in vivo, its effect on leukocyte migration across the blood-brain barrier was examined.
Results: Natalizumab specifically binds to CD49d, blocks the interaction between α₄β₁ and VCAM-1, and inhibits the infiltration of lymphocytes, B cells, and other cells into the central nervous system (CNS). [2]

Methods: AppKI mice bearing PTEN-CaP8 prostate cancer tumors and treated with ADT were administered natalizumab (62.5 μg, intraperitoneally, twice weekly), with isotype IgG serving as the control.
Results: Natalizumab effectively blocked α4 integrin-mediated immune cell adhesion and migration. Furthermore, Natalizumab repaired blood-brain barrier (BBB) damage, reduced immune infiltration in the brain, alleviated neuroinflammation and gliosis, and significantly improved ADT-exacerbated cognitive deficits. [3]

Human

Monoclonal

Unconjugated