Immunotherapy with anti-HER2 antibodies has been emerging to be promising for patients with HER2-positive breast cancer. With the recent reports of characterization with mouse monoclonal antibody that has been against HER2, they bind to the epitope different from the trastuzumab recognition and specifically plays a role in inhibiting the proliferation of tumor cells overexpressing HER2.
HER2 – A Overview
The HER2 proto-oncogene encodes the receptor tyrosine kinase that is overexpressed in a varied number of solid tumors. The amplification of the gene has led to correlate the poor prognosis in patients with breast cancer. Immunotherapy with HER2 antibody has shown potential results in patients with positive breast cancer HER2. The HER2, aka ErbB2, is located on chromosome 17 and encodes about 135kDa transmembrane glycoprotein.
HER2 is the reason for breast cancer in 30% of women, associated with protein expression and poor prognosis. The HER2 has been accessible and suitable as a target for cancer immunotherapy with its oncogenic potential by the use of monoclonal antibodies. Trastuzumab is the very first humanized monoclonal antibody approved for therapeutic use in breast cancer patients with overexpression HER2.
Discussion on Chimeric Antibody Against HER2
Monoclonal antibodies are an important part of biological drug discovery and represent the progressing pharmaceutical industry. About 26 monoclonal antibodies are existent in the industry with FDA approval and over 200 are constructed that are yet to be approved. With the early success of the mouse monoclonal antibodies that are developing their place in the therapeutic applications.
With the unique approach of Chimeric Antibody, the process of chimerization has the potential reducing the immunogenicity of the mouse monoclonal antibody applied for human treatment. HER2 gene overexpression has been noted for certain number of human malignancies, and have been proven as a important therapeutic target.
The mouse mAbs when chimerized and turning humanized, they are designed to be trastuzumab and pertuzumab. With trastuzumab being humanized mAb, it binds to the extracellular domain IV, HER2, thus inducing downregulation. For patients with metastatic breast cancer patients, the ones who respond to trastuzumab begin to demonstrate disease progression about a year from start.
New monoclonal antibodies generated with target specificity are novel to the extracellular domain of HER2. Pertuzumab is a combination therapy that is added with trastuzumab. The pertuzumab, another humanized monoclonal antibody, that binds to domain II of the HER2.
The purified chimeric antibody has the potential to specifically bind to HER2 positive brest cancer tumor cells. The binding of the chimeric antibody to the tumor specific cell inhibits the further proliferation of them. Thus, chimeric antibody or anti-HER2 monoclonal antibody is proven valuable for targeted immunotherapy for HER2 positive malignant cells.
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