Recombinant HER2 Antibody

Recombinant human anti-HER2 antibodies are a class of therapeutic proteins designed to target the human epidermal growth factor receptor 2 (HER2). HER2 is a member of the ErbB family of receptor tyrosine kinases, which play a crucial role in the regulation of cell growth and differentiation. Overexpression of HER2 is observed in approximately 20-30% of breast cancers and is associated with aggressive tumor growth and poor prognosis .

HER2, also known as ErbB2, is a ligand-less receptor that forms heterodimers with other members of the ErbB family, such as HER1 (EGFR), HER3, and HER4. This dimerization leads to the activation of downstream signaling pathways that promote cell proliferation and survival . In normal cells, HER2 expression is tightly regulated, but in cancer cells, gene amplification or protein overexpression leads to uncontrolled cell growth and tumor development .

The development of recombinant human anti-HER2 antibodies was driven by the need for targeted therapies that could specifically inhibit the activity of HER2 in cancer cells. Trastuzumab (Herceptin) was the first humanized monoclonal antibody approved for the treatment of HER2-positive breast cancer . Trastuzumab binds to the extracellular domain of HER2, preventing receptor dimerization and subsequent activation of downstream signaling pathways . Additionally, trastuzumab induces antibody-dependent cellular cytotoxicity (ADCC), leading to the destruction of cancer cells .

Recombinant human anti-HER2 antibodies, such as trastuzumab, work through multiple mechanisms to inhibit tumor growth:

1. Inhibition of HER2 Signaling: By binding to the extracellular domain of HER2, these antibodies prevent the receptor from dimerizing with other ErbB family members, thereby blocking the activation of downstream signaling pathways that promote cell proliferation and survival .
2. Induction of ADCC: The Fc region of the antibody interacts with immune cells, such as natural killer (NK) cells, leading to the targeted killing of HER2-overexpressing cancer cells .
3. Inhibition of HER2 Shedding: Trastuzumab has been shown to inhibit the proteolytic cleavage of HER2, preventing the release of the extracellular domain and the formation of a truncated, active receptor fragment known as p95HER2 .

Recombinant human anti-HER2 antibodies have shown significant clinical benefits in the treatment of HER2-positive breast cancer. Trastuzumab, in combination with chemotherapy, has been demonstrated to improve overall survival and reduce the risk of disease recurrence in patients with early-stage and metastatic HER2-positive breast cancer . Other anti-HER2 antibodies, such as pertuzumab and ado-trastuzumab emtansine (T-DM1), have also been developed and approved for clinical use .

Ongoing research aims to develop novel anti-HER2 therapies with improved efficacy and reduced resistance. Bispecific antibodies, which can simultaneously target HER2 and another receptor, are being investigated for their potential to enhance anti-tumor activity . Additionally, antibody-drug conjugates (ADCs) that deliver cytotoxic agents directly to HER2-overexpressing cancer cells are being explored as a means to improve therapeutic outcomes .