Gemtuzumab ozogamicin

Identification

Name
Gemtuzumab ozogamicin
Accession Number
DB00056 / 93NS566KF7
Groups
Mylotarg
Description

Gemtuzumab ozogamicin is a recombinant humanized IgG4 kappa antibody that's conjugated with calicheamicin spinoff, a cytotoxic antitumor antibiotic isolated from fermentation of Micromonospora echinospora ssp. calichensis. Gemtuzumab ozogamicin has about 50% of the antibody loaded with four-6 moles calicheamicin according to mole of antibody [FDA Label]. The antibody is specifically directed in opposition to the CD33 antigen present on leukemic myeloblasts in most sufferers with acute myeloid leukemia (AML). through binding to the CD33 antigen on tumors, the cytotoxic agent blocks the growth of cancerous cells and causes mobile death. advertising approval of gemtuzumab ozogamicin was granted on may also 17, 2000 by FDA as a treatment for patients with CD33-fine AML in first relapse who're 60 years of age or older and who are not taken into consideration applicants for cytotoxic chemotherapy [A98]. but, it turned into voluntarily withdrawn from the marketplace in 2010 because of protection concerns, elevated affected person deaths and inadequate evidence of clinical advantage at some point of confirmatory trials [L941]. On September 1 2017, gemtuzumab ozogamicin become again accepted for the remedy of adults with newly diagnosed CD33-positive acute myeloid leukemia but with a lower dosing regimen and a one of a kind time table in aggregate with chemotherapy or on its personal [L941]. it's also indicated for the treatment of patients elderly 2 years and older with CD33-high-quality AML who've skilled a relapse or who have not spoke back to preliminary remedy (refractory) [L941].

Pharmacology

Pharmacodynamics

Used for the treatment of acute myeloid leukemia (AML), mylotarg binds to the CD33 antigen, which is expressed on the surface of leukemic cells in more than 80% of patients with AML. The CD33 antigen is not expressed on pluripotent hematopoietic stem cells or nonhematopoietic cells. This gives mylotarg the selectivity needed to target leukemic cells.

Indication

Indicated for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. Indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory).

Action

Mylotarg is directed against the CD33 antigen expressed by hematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33 antigen results in the formation of a complex that is internalized. Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell. The released calicheamicin derivative binds to DNA in the minor groove resulting in site-specific DNA double strand breaks via formation of a p-benzene diradical [A20377]. Eventually, cell death is induced.