Anti-Human HER2 (Pertuzumab) (H290-GRP)

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.