Teplizumab

Teplizumab (MGA-031) is a Fc receptor non-binding anti-human CD3 monoclonal antibody. Teplizumab reduces the loss of beta-cell function. Teplizumab can be used in the research of type 1 diabetes[1][2].

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

CD3[1]

Teplizumab (10 ng/mL-10 μg/mL, 5 days) induces human CD8+ T-cell proliferation[3]. Teplizumab (6 days) increases the expression of CD25 and intracellular CTLA4 on CD8+ cells (freshly isolated PBMCs)[3]. Cell Proliferation Assay[1] Cell Line: Human PBMCs Concentration: 10 ng/mL, 100 ng/mL, 1 μg/mL, 10 μg/mL. Incubation Time: 5 days Result: Induced cell proliferation (measured by incorporation of [3H]thymidine in a 5-day assay.

Teplizumab (0.24 mg/kg, i.p.) induces migration of human CD4 T cells to the lamina propria and ablated the treatment effects of the drug on graft survival in NSG mice[2]. Animal Model: NOD/SCID IL2γc-/- (NSG) mice (a tolergenic humanized mouse model)[1] Dosage: 0.24 mg/kg, 5 μg Administration: Intraperitoneal injection (i.p.) Result: Decreased CD4:CD8 ratio in the peripheral blood from 2.03 to 1.01, p < 0.05. Decreased circulating hCD4 cells in the peripheral blood. Decreased in the proportion of T cells in the bone marrow and lung. Increased in the total number of human CD45+ cells infiltrating the lamina propria of the small intestine.

[1]. Kevan C Herold, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019 Aug 15;381(7):603-613.

[2]. Frank Waldron-Lynch, et al. I Analysis of FcR non-binding anti-CD3 mAb in humanized mice identifies novel human gut tropic cells with regulatory function that are found in patients. Sci Transl Med. 2012 Jan 25;4(118):118ra12.

[3]. Brygida Bisikirska, et al. TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J Clin Invest. 2005 Oct;115(10):2904-13.