Brentuximab

Brentuximab vedotin (cAC10-vcMMAE) is an antibody-drug conjugate (ADC) comprising an anti-CD30 antibody and the cytotoxic agent Monomethyl auristatin E (MMAE). Brentuximab vedotin inhibits CD30-positive cells with an IC50 of 2.5 ng/mL. Brentuximab vedotin can be used for the research of relapsed and refractory Hodgkin lymphoma[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

IC50: 2.5 ng/mL (CD30)

Brentuximab vedotin (cAC10-vcMMAE) (1 μg/mL; 96 h) has cytotoxicity to CD30+ in Karpas 299 cells[2]. .Brentuximab vedotin (CAC10-VCMMAE) (1 μg/mL; 12, 24 and 48 h) selectively induces growth arrest in G2/M phase then lead to apoptotic cell death[2]. . Cell Cytotoxicity Assay[2] Cell Line: Karpas 299 cells Concentration: 1 μg/mL Incubation Time: 96 h Result: Potently cytotoxic to CD30+ Karpas 299 cells, with an IC50 value of 2.5 ng/mL. Cell Cycle Analysis[2] Cell Line: L540 cells Concentration: 1 μg/mL Incubation Time: 12, 24, and 48 h Result: Selectively induced growth arrest in G2/M phase by apoptotic cell death.

Brentuximab vedotin (cAC10-vcMMAE) (10 to 120 mg/kg; intravenous injection; monitor for 3 weeks) to determine the maximum tolerated dose (MTD) is between 30 and 40 mg/kg[2]. Brentuximab vedotin (cAC10-vcMMAE) (0.3, 1 mg/kg; flanks injection; every 4 days for a total of 4 doses 1 mg/kg) can induce tumor CD30 regression[2]. Animal Model: SCID mice[2] Dosage: 10 to 120 mg/kg Administration: Intravenous injection; 10 to 120 mg/kg; for 3 weeks Result: Maximum tolerated dose (MTD) was between 30 and 40 mg/kg. Animal Model: SCID mice[2] Dosage: 0.3, 1 mg/kg Administration: Flanks injection; 1 mg/kg every 4 days for a total of 4 doses; 0.3 mg/kg every 4 days for a total of 4 doses Result: Induced complete, durable tumor regression, but 0.3 mg/kg provided lower therapy than 1 mg/kg dose.

[1]. Shea L, Mehta-Shah N. Brentuximab Vedotin in the Treatment of Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma. Curr Hematol Malig Rep. 2020 Feb;15(1):9-19.

[2]. Francisco JA, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65.