Tigatuzumab Overview

Introduction of Tigatuzumab

Tigatuzumab is a humanized IgG1 type monoclonal antibody agonists derived from TRA-8 with potential antitumor activity. It was developed by Tong Zhou, M.D., associate professor of medicine and cell biology and scientist at the UAB Comprehensive Cancer Center, in partnership with Daiichi-Sankyo Co. Ltd. of Japan. This drug is designed against tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), which is the limited expression in normal tissues but overexpressed in many kinds of tumors, including colon, gastric, pancreatic, lung, and cervical.

Tigatuzumab has been studied in many clinical trials for the treatment of cancers. A study in murine xenograft models has been demonstrated the tigatuzumab cytotoxicity in vitro and in vivo antitumor and efficacy of to a wide range of solid tumors. A phaseⅡ placebo-controlled trial of tigatuzumab in combination with carboplatin/paclitaxel in patients with chemotherapy-naïve metastatic/unresectable non-small cell lung cancer (NSCLC) has controlled, however, results data showed that tigatuzumab was well tolerated but did not improve the efficacy of carboplatin/paclitaxel in systemic therapy-naïve, unselected advanced NSCLC patients. Another phase Ⅱ study of in combination with gemcitabine in chemotherapy-naive patients with unresectable or metastatic pancreatic cancer began in 2013. As for breast cancer, a phase II trial of nanoparticle albumin-bound paclitaxel with or without the anti-death receptor 5 (DR5) monoclonal antibody tigatuzumab in patients with metastatic triple negative breast cancer has been carried out by Andres Forero-Torres. Tigatuzumab also has been investigated in patients with metastatic colorectal cancer to study how biodistribution, quantitative tumor uptake, and the antitumor response was impacted.

Mechanism of Action of Tigatuzumab

Tigatuzumab 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 mainly expressed by the immune system cells and belongs to the tumor necrosis factor family of cytokines. TNFRSF10B acts as a death receptor that transmits apoptotic signals through different signaling systems to induce apoptosis when stimulated by the external apoptotic initiator. TNFRSF10B consists of two parts, the extracellular part 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 tigatuzumab mimics the interaction between native TRAIL and TNFRSF10B. When the administration, tigatuzumab binds to TNFRSF10B and induces tumor cells apoptosis through cellular caspases signal.

Fig.1 Mechanism of action of Tigatuzumab

What We Provide

Therapeutic Antibody

Tigatuzumab

We provide high-quality Tigatuzumab 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.