Drozitumab Overview

Introduction of Drozitumab

Drozitumab is a human monoclonal antibody directed against tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), a member of tumor necrosis factor related apoptosis-inducing ligand (TRAIL). It was developed by Genentech as a drug for the treatment of cancers. This drug has been investigating in various trials for treating cancers including chondrosarcoma, colorectal cancer, non-Hodgkin lymphoma, and non-small cell lung cancer. The efficacy and selectivity of drozitumab in rhabdomyosarcoma (RMS) has been evaluated in preclinical models. And results showed that drozitumab is effective, in vitro, against the majority of RMS cell lines that express caspase-8 and, in vivo, may provide long-term control of RMS. In preclinical glioblastoma models, drozitumab has been found to induce apoptosis and colony formation in several glioblastoma cell lines combined with BV6 (combination index<0.1). A study about triple-negative breast cancer reported that drozitumab could induce apoptosis in mesenchymal TNBC cell lines but not in cell lines from other breast cancer subtypes. The previous study about the treatment of pancreatic ductal adenocarcinoma has revealed that drozitumab could selectively eliminate CSCs, resulting in tumor growth inhibition and even regression of pancreatic tumors.

Mechanism of Action of Drozitumab

Drozitumab is a human Immunoglobulin G1 (IgG1) monoclonal agonist directed against TNFRSF10B, which is also known as death receptor 5 (DR5) and tumor necrosis factor related apoptosis-inducing ligand receptor 2 (TRAIL-R2). TNFRSF10B is a member of the tumor necrosis factor family of cytokines and expressed mainly by cells of the immune system. TNFRSF10B is one of the five death receptors, which are stimulated by the external apoptotic initiator and transmit apoptotic signals through different signaling systems to induce apoptosis. Just like other members of TFN superfamily, the extracellular part of TNFRSF10B is a cysteine-rich region, and the intracellular region is a death domain with hydrolytic function, which is responsible for the trigger of intracellular apoptosis signal. When TNFRSF10B binds to its ligand, Fas-associated death domain (FADD) is recruited. FADD forms the death induced signal complex (DISC) with procaspase 8 through its N-terminal death effector domain (DED), stimulating and activating caspase-8 and caspase-10. After activation, caspase-8 catalyzes caspase protease to produce cascade amplification reaction, and finally plays the biological function of inducing cell apoptosis by activating its effector caspase-3. Diseases associated with TNFRSF10B include squamous cell carcinoma, head and neck, and diffuse infiltrative lymphocytosis syndrome. And the related pathways TNFRSF10B involved in include gene expression and protein kinase B (Akt) signaling.TNFRSF10B is expressed on a variety of solid tumors and cancers of hematopoietic origin. In addition, it is more widely expressed on the surface of tumor cells than normal cells, and when it binds to related ligands, it can selectively kill a variety of tumor cells and is less toxic to normal cells. Therefore, TNFRSF10B has become the most ideal target molecule for developing anti-tumor specific monoclonal antibody drugs. The mechanism of action of drozitumab mimics the interaction between native TRAIL and TNFRSF10B. When the administration, drozitumab binds to TNFRSF10B and induces tumor cells apoptosis through cellular caspases signal.

Fig.1 Mechanism of action of Drozitumab

What We Provide

Therapeutic Antibody

Drozitumab

We provide high-quality Drozitumab 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.

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