Yao Heng Huang
Antibodies are a class of protein drugs that display great potential in treating disease due to their good affinity and their long half-lives. If done properly like in drugs like trastuzumab, they have the potential to be a treatment for many diseases with efficacious results and low side effects. My name is Yao Heng Huang and I'm currently a senior in the pharmaceutical science program working under Dr. Dhaval K. Shah. Dr.Shah's lab specializes in antibodies and protein engineering and my project was to humanize a chimeric antibody for the Receptor for Advanced Glycation or RAGE found in some forms of cancer such as colorectal cancer. The immunogenicity of chimeric antibodies can be very detrimental and can lead to the body rejecting the drug and many side effects. By using CDR grafting, I hope to humanize the chimeric antibody while retaining its affinity.
The receptor for advanced glycation end products (RAGE) is a 35kDa receptor in the immunoglobulin protein which is overexpressed in tumors of certain cancers such as breast, and colon cancers. RAGE is not expressed anywhere else in the human body except for a specific subtype in the lung which makes it ideal for an antibody target. The technique of CDR grafting is to humanize the antibodies. These regions were grafted onto an appropriate human framework to humanize it determined through homology and structural analysis of the antibody. The framework which will be used is determined using homology to be close as possible to the rabbit sequence to retain the affinity for the antigen. Once the CDR regions have been identified, spliced and attached to the appropriate framework, affinity studies will be conducted to determine its affinity to the RAGE receptor and the immunogenicity.
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