VivoGenie Anti-Human HER2 (Pertuzumab) - Fc Reduced (IVMB0416)

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.