Anti-Human HER2 (Pertuzumab)
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Antibody DetailsProduct DetailsReactive Species Human Expression Host HEK-293 Cells FC Effector Activity Active Recommended Isotype Controls Immunogen Humanized antibody derived from mouse clone 2C4. 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. Storage and Handling Functional grade biosimilar 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 -80°C. Avoid Repeated Freeze Thaw Cycles. Regulatory Status Research Use Only (RUO). Non-Therapeutic. Country of Origin USA Shipping 2-8°C Wet Ice Additional Applications Reported In Literature ? ELISA FA N IP IF FC Antagonist Each investigator should determine their own optimal working dilution for specific applications. See directions on lot specific datasheets, as information may periodically change. DescriptionDescriptionSpecificity Pertuzumab binds specifically to human and cynomolgus HER2 near the center of extracellular domain II of the dimerization arm, adjacent to the binding pocket used for receptor dimerization. Background HER2 (ERBB2) is a member of the epidermal growth factor (EGF) family of receptor tyrosine kinases that regulate cell growth, survival and differentiation 1,2. HER2 activates downstream signaling pathways by forming a heterodimer with other ligand-bound EGF receptor family members (EGF receptor, HER3, HER4). Dysregulation of HER2 contributes to tumorigenesis in breast, ovarian, gastric, and other cancers 1. Additionally, HER2-HER3 heterodimers are potent signaling dimers required for HER2-mediated cancer cell proliferation 3.
Pertuzumab is a humanized monoclonal antibody used in the treatment of breast cancers that have either HER2 protein overexpression or ERBB2 gene amplification 2. Pertuzumab blocks HER2 function as a coreceptor by sterically inhibiting its heterodimerization with other HER family members, including EGF receptor, HER3, and HER4 3,4,5,6. As a result, HER2’s ability to activate pathways associated with cancer cell proliferation and survival is limited 2. Additionally, when pertuzumab binds to a cancer cell, antibody-dependent cellular cytotoxicity is triggered. Pertuzumab is a full-length, chimeric IgG1 antibody generated by cloning VLκI and VHIII of murine 2C4 into a vector containing human kappa and CH1 domains 7. Pertuzumab was initially expressed and purified as a Fab from E. coli for residue optimization and subsequently was stably produced in Chinese hamster ovary cells. Contact between pertuzumab and HER2 occurs at the HER2 heterodimerization interface 4 and is primarily made with the heavy chain of the antibody fragment, with a small contribution from the light chain 8. Additionally, Leu295 and His296 are important for binding. Antigen Distribution HER2 is ubiquitously expressed in epithelial, mesenchymal, and neuronal cells and their cellular progenitors. It is mostly localized to the plasma membrane and is generally excluded from clathrin-coated pits. Ligand/Receptor EGF receptors, SHC1, c-Src, Integrin B4, Grb2, SOS1, JAK2 NCBI Gene Bank ID UniProt.org Research Area Biomarker . Biosimilars . Cancer . Immunology References & Citations1. https://www.ncbi.nlm.nih.gov/gene/2064 2. Dean L, Kane M. Pertuzumab Therapy and ERBB2 Genotype. 2015 Sep 10 [Updated 2021 Jan 21]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK315949/ 3. Metzger-Filho O, Winer EP, Krop I. Clin Cancer Res. 19(20):5552-5556. 2013. 4. Franklin MC, Carey KD, Vajdos FF, et al. Cancer Cell. 5(4):317-328. 2004. 5. Hughes JB, Berger C, Rødland MS, et al. Mol Cancer Ther. 8(7):1885-1892. 2009. 6. Keating GM. Drugs. 72(3):353-360. 2012. 7. Adams CW, Allison DE, Flagella K, et al. Cancer Immunol Immunother. 55(6):717-727. 2006. 8. Roskoski R Jr. Pharmacol Res. 79:34-74. 2014. 9. Tanner M, Kapanen AI, Junttila T, et al. Mol Cancer Ther. 3(12):1585-1592. 2004. 10. Friess T, Scheuer W, Hasmann M. Clin Cancer Res. 11(14):5300-5309. 2005. 11. Nahta R, Yuan LX, Zhang B, et al. Cancer Res. 65(23):11118-11128. 2005. 12. Erjala K, Sundvall M, Junttila TT, et al. Clin Cancer Res. 12(13):4103-4111. 2006. 13. Arpino G, Gutierrez C, Weiss H, et al. J Natl Cancer Inst. 99(9):694-705. 2007. 14. Osipo C, Meeke K, Cheng D, et al. Int J Oncol. 30(2):509-520. 2007. 15. Sakai K, Yokote H, Murakami-Murofushi K, et al. Cancer Sci. 98(9):1498-1503. 2007. 16. Nagumo Y, Faratian D, Mullen P, et al. Mol Cancer Res. 7(9):1563-1571. 2009. 17. Scheuer W, Friess T, Burtscher H, et al. Cancer Res. 69(24):9330-9336. 2009. 18. Sak MM, Szymanska M, Bertelsen V, et al. Carcinogenesis. 34(9):2031-2038. 2013. 19. Yamashita-Kashima Y, Shu S, Harada N, et al. Oncol Rep. 30(3):1087-1093. 2013. 20. Zahnd C, Pecorari F, Straumann N, et al. J Biol Chem. 281(46):35167-35175. 2006. 21. Fábián Á, Horváth G, Vámosi G, et al. Cytometry A. 83(4):375-385. 2013. Technical ProtocolsCertificate of Analysis |
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H290 | |
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Products are for research use only. Not for use in diagnostic or therapeutic procedures.