In this article, we will discuss Gemtuzumab Ozogamicin (Mechanism of Action). So, let’s get started.
Mechanism of Action
Gemtuzumab ozogamicin is a CD33-directed antibody-drug conjugate (ADC). The antibody portion (hP67.6) recognizes human CD33 antigen. The small molecule, N-acetyl gamma calicheamicin, is a cytotoxic agent that is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of gemtuzumab ozogamicin is due to the binding of the ADC to CD33-expressing tumor cells, followed by
internalization of the ADC-CD33 complex, and the intracellular release of N-acetyl gamma calicheamicin dimethyl hydrazide via hydrolytic cleavage of the linker. Activation of N-acetyl gamma calicheamicin dimethyl hydrazide induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death.
Saturation of a high percentage of CD33 antigenic sites is presumed to be required for maximum delivery of calicheamicin to leukemic blast cells. Near maximal peripheral CD33 saturation was observed across studies after gemtuzumab ozogamicin dosing at dose levels of 2 mg/m² and above. At 9 mg/m² gemtuzumab ozogamicin (2 doses, 14 days apart), the risk for VOD increases as the Cmax of the first dose of gemtuzumab ozogamicin increases. The increase in VOD is more prominent in patients with prior stem cell transplantation.