Anti-Human Mesothelin (Amatuximab)

Mesothelin cDNA on mesothelin-positive cells

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.

Liquid

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.

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.

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.

Research Use Only

2 – 8° C Wet Ice

This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Amatuximab. MORAb-009 (Amatuximab) is a chimeric, humanized monoclonal antibody that targets cell surface human and cynomolgus monkey mesothelin. Amatuximab does not cross-react with rat or mouse mesothelin.

Mesothelin is involved in normal cell adhesion, differentiation, and signal transduction processes¹. In cancer, mesothelin is involved in proliferation, cell migration, and inhibition of apoptosis, making mesothelin a target for cancer therapy. Mesothelin binds to the cancer antigen MUC16 (CA-125), and this interaction may promote cell adhesion and metastasis.

MORAb-009 (Amatuximab) was generated by panning a phage display library created by immunizing a mouse with mesothelin cDNA on mesothelin-positive cells^2,3. A mouse precursor antibody was identified, isolated, and its affinity optimized by engineering its variable regions to derive SS1 (scFV). The gene encoding mesothelin Fv (SS1 scFv) was then fused with human IgG1 and kappa regions to form a chimeric antibody.

Amatuximab binds mesothelin on the cell surface of ovarian, mesothelioma, and pancreatic cancer cell lines². Amatuximab also stains neoplastic cells using immunohistochemistry techniques. Amatuximab is internalized upon binding mesothelin at the cell surface. Additionally, amatuximab enhances antibody-dependent cytotoxicity in mesothelin positive cancer cell lines and inhibits interaction of mesothelin-expressing cells with MUC16-expressing cells. Preliminary epitope mapping shows that Amatuximab binds mesothelin at its amino terminus.

Mesothelin (also known as CAK1) is a cell surface glycoprotein found on normal mesothelial cells, including pleura, pericardium, fallopian tubes, trachea, and cornea. Mesothelin is overexpressed by cells in mesothelioma, ovarian cancer, pancreatic cancer, acute myeloid leukemia, and cholangiocarcinoma. Mesothelin has both membrane-bound and soluble forms.

CA125/MUC16

1 Baldo P, Cecco S. Onco Targets Ther. 10:5337-5353. 2017.
2 Hassan R, Ebel W, Routhier EL, et al. Cancer Immun. 7:20. 2007.
3 Chowdhury PS, Viner JL, Beers R, et al. Proc Natl Acad Sci U S A. 95(2):669-674. 1998.
4 Fujisaka Y, Kurata T, Tanaka K, et al. Invest New Drugs. 33(2):380-388. 2015.