ozogamicin

Ozogamicin refers to the cytotoxic payload used in certain antibody-drug conjugates (ADCs) derived from the calicheamicin family of antibiotics. The best-known ozogamicin-containing drug is gemtuzumab ozogamicin (GO), an ADC designed to target CD33 on acute myeloid leukemia (AML) cells. The active calicheamicin component was originally isolated from the bacterium Micromonospora echinospora.

The mechanism of action involves the ADC binding to CD33 on leukemic cells, followed by internalization. After the linker is cleaved inside the cell, the calicheamicin gamma1I moiety is released and induces double-strand breaks in DNA, triggering apoptosis. The antibody component directs the cytotoxin to malignant cells, helping to limit exposure of healthy tissues.

In medical use, GO received FDA approval in 2000 for AML but safety concerns led to its withdrawal from the U.S. market in 2005. It was reintroduced in 2017 at a lower dose and with restricted indications, and its use varies by regulatory region and treatment setting.

Adverse effects of ozogamicin-containing therapies include hepatotoxicity, particularly veno-occlusive disease, as well as myelosuppression, infections, infusion reactions, and cytopenias. Careful patient selection and monitoring are important to balance potential benefits with risks.

Chemically, the therapy is an antibody-drug conjugate in which an anti-CD33 monoclonal antibody is linked to calicheamicin gamma1I via a covalent linker that releases the toxin within target cells. The term ozogamicin refers to this calicheamicin-based payload used in such conjugates.

See also: calicheamicin, antibody-drug conjugate, Mylotarg.