Glembatumumab vedotin (CDX-011) is an ADC (antibody-drug conjugates (ADCs)) comprising a fully human IgG2 monoclonal antibody (CR011) directed against glycoprotein NMB (GPNMB) and conjugated to the potent tubulinbinding cytotoxic agent MMAE via a protease-sensitive vc linker. Glembatumumab vedotin has potent anticancer effects.
Glembatumumab vedotin binds to GPNMB on tumors, the complex is internalized and MMAE is released via proteolytic cleavage of the vc linker in a lysosomal compartment. Tumor cell death occurs as a result of microtubule inhibition by MMAE with resultant cell cycle arrest[1].Glembatumumab vedotin (1-125 μg/mL; 96 hours) demonstrates osteosarcoma cytotoxic activity[3].
Glembatumumab vedotin (CR011-vcMMAE; 1.25-80 mg/kg; i.v.; every 4 days; for 16 days) shows short-term anti-tumor effects (inhibition of tumor growth) and long-term effects (complete regression) in human SK-MEL-2 and SK-MEL-5 melanoma xenografts[2].
References:
[1]. Christopher H Keir, et al. The use of an antibody drug conjugate, glembatumumab vedotin (CDX-011), for the treatment of breast cancer. Expert Opin Biol Ther. 2012 Feb;12(2):259-63.
[2]. Vincent A Pollack, et al. Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB. Cancer Chemother Pharmacol. 2007 Aug;60(3):423-35.
[3]. Michael Roth, et al. Targeting Glycoprotein NMB With Antibody-Drug Conjugate, Glembatumumab Vedotin, for the Treatment of Osteosarcoma. Pediatr Blood Cancer. 2016 Jan;63(1):32-8.