Anti-Human CD33 (Gemtuzumab) – Fc Muted™
Anti-Human CD33 (Gemtuzumab) – Fc Muted™
Product No.: C1045
Product No.C1045 Clone hP67.6 Target CD33 Product Type Biosimilar Recombinant Human Monoclonal Antibody Alternate Names SIGLEC-3, SIGLEC3, p67, gp67 Isotype Human IgG4κ Applications ELISA , FC , IF , WB |
Antibody DetailsProduct DetailsReactive Species Human Host Species Human Expression Host HEK-293 Cells FC Effector Activity Muted Immunogen Humanized antibody derived from mouse clone P67.6 Product Concentration ≥ 5.0 mg/ml Endotoxin Level < 1.0 EU/mg as determined by the LAL method Purity ≥95% by SDS Page ⋅ ≥95% monomer by analytical SEC Formulation This biosimilar antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration. State of Matter Liquid Product Preparation Recombinant biosimilar antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates. Pathogen Testing To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s recombinant biosimilar antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile. Storage and Handling 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. Regulatory Status Research Use Only Country of Origin USA Shipping 2-8°C Wet Ice Additional Applications Reported In Literature ? ELISA, WB, IF, FC Each investigator should determine their own optimal working dilution for specific applications. See directions on lot specific datasheets, as information may periodically change. DescriptionDescriptionSpecificity This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Gemtuzumab but is not covalently linked to Calich-DMH. This product is for research use only. Gemtuzumab antibody activity is directed against CD33. Background 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. Antigen Distribution CD33 is expressed on normal multipotent myeloid precursor cells,
unipotent colony-forming cells, maturing granulocytes and monocytes, macrophages, dendritic
cells, and can be displayed on subsets of B cells, activated T cells and natural killer cells. CD33
is also expressed on the surface of leukemic cell blasts in more than 90% of patients with acute
myeloid leukemia, but is not present on normal stem cells. Ligand/Receptor sialic acid residues NCBI Gene Bank ID UniProt.org Research Area Autoimmune . Biosimilars . Cancer . Immunology . Inflammatory Disease Leinco Antibody AdvisorPowered by AI: AI is experimental and still learning how to provide the best assistance. It may occasionally generate incorrect or incomplete responses. Please do not rely solely on its recommendations when making purchasing decisions or designing experiments. Research-grade Gemtuzumab biosimilars are commonly used as calibration standards or reference controls in pharmacokinetic (PK) bridging ELISAs to quantitatively measure drug concentration in serum samples, provided there is demonstrated analytical equivalence between the biosimilar and reference material. To ensure the assay accurately measures Gemtuzumab concentrations for both biosimilar and reference (originator) products, the following steps and rationale typically apply:
Key technical implementation details:
In summary: Primary in vivo models for evaluating anti-CD33 antibodies in tumor growth inhibition and TIL characterization are human xenograft models, particularly using immunodeficient mice engrafted with human AML cells, and, less commonly, humanized mouse models. Syngeneic models are standard for immunotherapy studies and TIL analysis but are not used for anti-CD33 antibodies unless the tumor expresses CD33 and the antibody is cross-reactive to murine CD33. Model Types Utilized:
TIL Characterization:
Summary Table
Key references for anti-CD33 antibodies in vivo:
In summary, anti-CD33 research-grade antibodies are administered principally in human AML xenograft models and, less frequently, humanized mice. TIL analysis is possible and routine in syngeneic models for immunotherapy, but anti-CD33 antibody use in these models is uncommon due to antigen specificity limitations. Researchers investigating synergistic effects in complex immune-oncology models often use Gemtuzumab biosimilars—which target CD33-positive leukemic cells—alongside other checkpoint inhibitor biosimilars (such as anti-CTLA-4 or anti-LAG-3) to assess how multiple immune pathways can be modulated simultaneously. This combination approach helps to elucidate whether targeting more than one immune mechanism can enhance antitumor activity beyond what is achievable with monotherapy. Key elements of these investigations:
Synergy evaluation:
Challenges in biosimilar research:
Summary table: Gemtuzumab Biosimilar + Checkpoint Inhibitor Combinations
This multifaceted approach is increasingly central in studies aiming to overcome resistance and improve outcomes in complex cancers like AML by engaging both direct cytotoxicity and immune-system reactivation. A Gemtuzumab biosimilar can be used as both the capture and detection reagent in a bridging ADA ELISA to detect anti-drug antibodies (ADAs) that develop in response to gemtuzumab therapy in patients with AML. Bridging ADA ELISA works as follows:
Key details for using a biosimilar in this assay:
Applications:
Additional notes:
In summary, Gemtuzumab biosimilar is both plate-bound (capture) and labeled (detection) in bridging ADA ELISA, allowing sensitive detection of patient antibodies directed against the therapeutic gemtuzumab. References & Citations1 Clark MC, Stein A. Best Pract Res Clin Haematol. 33(4):101224. 2020. 2 McGavin JK, Spencer CM. Drugs. 61(9):1317-1322; discussion 1323-4. 2001. 3 Hamann PR, Hinman LM, Hollander I, et al. Bioconjug Chem. 13(1):47-58. 2002. 4 Thota S, Advani A. Eur J Haematol. 98(5):425-434. 2017. 5 Naito K, Takeshita A, Shigeno K, et al. Leukemia. 14(8):1436-1443. 2000. 6 Matsui H, Takeshita A, Naito K, et al. Leukemia. 16(5):813-819. 2002. 7 Takeshita A, Shinjo K, Naito K, et al. Leukemia. 19(8):1306-1311. 2005. 8 Larson RA, Sievers EL, Stadtmauer EA, et al. Cancer. 104(7):1442-1452. 2005. Technical ProtocolsCertificate of Analysis |
Formats Available
Prod No. | Description |
---|---|
C1040 | |
C1045 |
