Anti-Human CD33 (Gemtuzumab) - 25 mg

Recombinant Antibodies>Biosimilar Recombinant Antibodies|Primary Monoclonal Antibodies

2 - 8°C Wet Ice

CD33 is a sialic-acid-binding immunoglobulin-like lectin (Siglec) that acts as an endocyticreceptor1. CD33 is considered an attractive target for conjugated antibody chemotherapeuticdevelopment in patients with acute myeloid leukemia (AML) because ~90% of patients expressCD33 surface antigen on myeloid blast cells, but not normal stem cells2, and additionally CD33is rapidly internalized when bound3.N-acetyl-γ-calicheamicin is a potent, natural cytotoxic agent produced by Micromonosporaechinospora that induces double-strand DNA breaks and apoptosis in rapidly proliferating cells, independent of cell cycle progression, and is therefore also of interest as a chemotherapeuticagent3, 4. The semisynthetic derivative N-acetyl-γ-calicheamicin dimethyl hydrazide (Calich-DMH; calicheamicin) is used as an enediyne antitumor antibiotic in CD33-based chemotherapy3.Gemtuzumab is an antibody-drug conjugate composed of Calich-DMH attached via acetylbutyrate linker to hP67.6, an anti-CD33 antibody humanized from its murine progenitor by CDRgrafting3. The conjugate contains a lysine attachment to the antibody as well as a hydrazonelinkage which allows for hydrolytic release. When Gemtuzumab binds CD33-expressing tumorcells, the Gemtuzumab-CD33 complex is rapidly internalized and the acidic intracellularenvironment (presumably in the endosomes/lysosomes of target cells) triggers the release ofCalich-DMH. Calich-DMH then binds to the minor groove of DNA, undergoes a structuralchange in its enediyne moiety that generates diradicals, and induces double-strand DNAbreakage, cell cycle arrest and apoptosis3, 4, 5. Gemtuzumab temporarily arrests NB4 cells, but notclinical samples, at the G2/M phase and increases the percentage of hypodiploid cells in celllines as well as clinical samples5, 6, 7. Gemtuzumab has a drug loading capacity of 2-3 mol ofCalich-DMH per mole of antibody3. However, the effects of Gemtuzumab are negativelyinfluenced by P-glycoprotein6.Gemtuzumab has been approved for treatment of some patients with relapsed acute myelomawho are aged 60 and over2.

≥ 5.0 mg/ml

CD33 is expressed on normal multipotent myeloid precursor cells, unipotent colony-forming cells, maturing granulocytes and monocytes, macrophages, dendriticcells, and can be displayed on subsets of B cells, activated T cells and natural killer cells. CD33is also expressed on the surface of leukemic cell blasts in more than 90% of patients with acutemyeloid leukemia, but is not present on normal stem cells.