Introduction of Metelimumab

Metelimumab (CAT-192) is a human IgG4 monoclonal antibody (mAb) that neutralizes transforming growth factor beta 1 (TGF-β1) which had been chosen for further development for the treatment of diffuse cutaneous systemic sclerosis, also known as scleroderma.

Mechanism of Action of Metelimumab

TGF-β1 is a polypeptide member of the transforming growth factor beta (TGF-β) superfamily of cytokines. TGF-β is a pleiotropic cytokine that is a member of a superfamily of ligands that includes bone morphogenetic proteins and activins. Under normal conditions, TGF-β helps to maintain homeostasis and limit the growth of epithelial, endothelial, neuronal, and hematopoietic cell lineages through anti-proliferative and apoptotic responses. In addition, TGF-β exerts potent effects that influence immune function, differentiation, adhesion, extracellular matrix production, cell motility, angiogenesis, and cytokine production. Early in the transition of premalignant lesions into malignant neoplasms, TGF-β can suppress cell growth; however, in advanced cancers these effects are typically lost. Instead, TGF-β will directly promote tumor growth and metastases. TGF-β-induced cellular changes have been described in many different tumor models and appear to be important for inducing cell migration and promoting metastases. TGFβ also attenuates host antitumor immune responses. With broad activity in natural killer (NK) cells, T cells including T regulatory cells, NKT cells, monocytes/macrophages, and dendritic cells, TGFβ can down-regulate both primary and secondary immune responses and suppress antitumor effector cells. Metelimumab binds to and inhibits the activity of all isoforms of TGF-β1, resulting in the inhibition of tumor cell growth, angiogenesis, and migration, and thereby shows its’ anti-tumor therapeutic efficacy.

Fig.1 Mechanism of action of Metelimumab

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