Gemtuzumab Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Gemtuzumab ozogamicin was launched as the first antibody-targeted
antineoplastic agent for treatment of patients with acute myeloid leukemia (AML). This
immunoconjugate consists of an anti-CD33 humanized mouse monoclonat antibody (lgG4)
linked via a bifunctional linker to the cytotoxic antibiotic calicheamicin. Once, the anti-CD33
binds to its antigen expressed on AML blast cells, a complex forms that is internalized,
eventually releasing the calicheamicin derivative inside the cell. The released antibiotic
binds to the minor groove of DNA and after Bergman cyclization induces double-strand
breaks and cell-death. Results from both phase I and II clinical trials suggested that this
drug, when administered (9 mg/m2 as 2 i.v. infusions separated by 14 days) as a single
agent to patients in first relapse, demonstrates an acceptable safety profile, while
achieving meaningful clinical remission in 32 to 43% of individuals. Gemtuzumab
ozogamicin is considered at least as effective as conventional therapy but presents a more
favorable tolerability profile as compared to standard chemo-therapeutic drugs commonly
used to treat AML. This agent received accelerated approval from the FDA for the
treatment of patients in first relapse who are 60 years of age or older and who are not
considered candidates for cytotoxic chemotherapy.
Verwenden
Treatment of relapsed, acute myelogenous leukemia (cytotoxic calicheamicin derivative conjugated to a humanized monoclonal antibody).
Allgemeine Beschreibung
Gemtuzumab ozogamicin (Mylotarg, fusion molecule) isan MAb derived from the CD33 antigen, a sialic aciddependentadhesion protein expressed on the surface ofleukemia blasts and immature normal cells of myelomonocyticorigin but not on normal hematopoietic stem cells. Gemtuzumab ozogamicin is indicated for the treatmentof patients with CD33-positive acute myeloid leukemia infirst relapse among adults 60 years of age or older who arenot considered candidates for cytotoxic chemotherapy.Gemtuzumab ozogamicin binds to the CD33 antigen expressedby hematopoietic cells. This antigen is expressed onthe surface of leukemic blasts in more than 80% of patientswith acute myeloid leukemia. CD33 is also expressed onnormal and leukemic myeloid colony-forming cells, includingleukemic clonogenic precursors, but it is not expressedon pluripotent hematopoietic stem cells or nonhematopoieticcells. Binding of the anti-CD33 antibody results in acomplex that is internalized. On internalization thecalicheamicin derivative is released inside the lysosomes ofthe myeloid cells. The released calicheamicin derivativebinds to the minor groove of DNA and causes double-strandbreaks and cell death.
Gemtuzumab Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
