Anti-Human CD33 (Gemtuzumab)

Catalogue Number: C1040-LET

Manufacturer:	Leinco Technologies, Inc
Type:	Recombinant Monoclonal
Shipping Condition:	Blue Ice
Unit(s):	1 mg, 100 mg, 25 mg, 5 mg, 50 mg
Host name:
Clone:	hP67.6
Isotype:
Immunogen:
Application:	ELISA, FC, IF, WB

Overview

Description

Description: CD33 is a sialic-acid-binding immunoglobulin-like lectin (Siglec) that acts as an endocytic receptor1. CD33 is considered an attractive target for conjugated antibody chemotherapeutic development in patients with acute myeloid leukemia (AML) because ~90% of patients express CD33 surface antigen on myeloid blast cells, but not normal stem cells2, and additionally CD33 is rapidly internalized when bound3. N-acetyl-γ-calicheamicin is a potent, natural cytotoxic agent produced by Micromonospora echinospora 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 chemotherapeutic agent3, 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 acetyl butyrate linker to hP67.6, an anti-CD33 antibody humanized from its murine progenitor by CDR grafting3. The conjugate contains a lysine attachment to the antibody as well as a hydrazone linkage which allows for hydrolytic release. When Gemtuzumab binds CD33-expressing tumor cells, the Gemtuzumab-CD33 complex is rapidly internalized and the acidic intracellular environment (presumably in the endosomes/lysosomes of target cells) triggers the release of Calich-DMH. Calich-DMH then binds to the minor groove of DNA, undergoes a structural change in its enediyne moiety that generates diradicals, and induces double-strand DNA breakage, cell cycle arrest and apoptosis3, 4, 5. Gemtuzumab temporarily arrests NB4 cells, but not clinical samples, at the G2/M phase and increases the percentage of hypodiploid cells in cell lines as well as clinical samples5, 6, 7. Gemtuzumab has a drug loading capacity of 2-3 mol of Calich-DMH per mole of antibody3. However, the effects of Gemtuzumab are negatively influenced by P-glycoprotein6. Gemtuzumab has been approved for treatment of some patients with relapsed acute myeloma who are aged 60 and over2.

Additional Text

Concentration

5 mg/ml

Antibody Clonality

Monoclonal, Recombinant Monoclonal

Storage Note

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Price

£121.00

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