Crizanlizumab Overview

Introduction of Crizanlizumab

Crizanlizumab (formerly SelG1), is a fully human IgG2κ type monoclonal antibody directed against P-selectin, which functions as a cell adhesion molecule (CAM). This drug was developed by Novartis and has been considered as a potential treatment of sickle cell anemia.

A phaseⅡtrial of crizanlizumab assesses its safety and effectiveness was conducted in 198 patients with sickle cell anemia. Results showed that crizanlizumab could significantly reduce sickle cell-related pain crises compared with placebo, associating with a low incidence of adverse events. Recently, a new PhaseⅡtrial has been conducted to further investigated the way crizanlizumab is absorbed, distributed and eliminated by the body, as well as its effects on the body at 5 mg/kg in about 45 adult patients with sickle cell anemia and vaso-occlusive pain events. Results showed the crizanlizumab could significantly lower the rate of VOC in patients with SCD by 45% compared to placebo. However, more clinical trials of crizanlizumab are still undergoing.

Mechanism of Action of Crizanlizumab

Crizanlizumab was made in the laboratory and designed to bind P-selectin, a protein that is found on the surface of endothelial cells (cells lining the inner walls of blood vessels) and in platelets. P-selectin is stored in α-granules of platelets and in Weibel–Palade bodies of endothelial cells when the platelets and endothelial cells are unactivated. P-selectin belongs to the selectins family, which contains three members (L-, E-, and P-selectin). Selectins are found to involved in various chronic and acute inflammation processes such as post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus, and cancer metastasis, as well as constitutive lymphocyte homing. The roles of selectin in inflammation and progression of cancer have been focused recently. It seems that tumor cells enhance distant organ metastasis, showing ‘leukocyte mimicry’, via the selectin-dependent mechanisms mediating cell tethering and rolling interactions. P-selectin, also known as CD62P, Granule Membrane Protein 140 (GMP-140), and Platelet Activation-Dependent Granule to External Membrane Protein (PADGEM), is the largest in the selectins family. The primary Ligand for P-selectin on eosinophils and neutrophils is P-selectin glycoprotein ligand-1 (PSGL-1; SELPLG), which is expressed on all white blood cells and plays important roles in the recruitment of white blood cells into inflamed tissue. A number of studies have shown that P-selectin interacts with circulating cancer cells at an early stage of metastasis in cancer dissemination. In addition, P-selectin is also found to play an important role in the initial recruitment of leukocytes (white blood cells) to the site of injury during inflammation and in in the recruitment and aggregation of platelets at areas of vascular injury. The function of P-selectin is to control the flow of white blood cells through blood vessels, and how they adhere to vessel walls, during periods of inflammation and tissue repair. And in sickle cell anemia, it is found to increase the rate of the adhesion of sickle red blood cells to blood vessels, preventing blood flow through smaller vessels and causing inflammation and pain crises. Crizanlizumab is an antibody-drug binds to P-selectin, blocking its interaction with PSGL-1 on neutrophils and monocytes. By inhibiting platelet aggregation, maintaining normal blood flow, this drug could minimize sickle cell-related pain crises (SCPC).

Fig.1 Mechanism of action of Crizanlizumab

Table 1. Clinical Projects of Crizanlizumab

What We Provide

Therapeutic Antibody

Crizanlizumab

We provide high-quality Crizanlizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Crizanlizumab

For research use only. Not intended for any clinical use.