Novel Monoclonal Antibody Technology Development
As the most significant recognition reagents in the immune system, monoclonal antibodies (mAbs) are widely used in research and medicine. Comparing to small molecule drugs, antibody therapeutics offer distinct advantages: higher specificity, better-understood mechanisms, and predictable safety. To date, more than 60 therapeutic antibodies have been approved and sales exceeded $106 billion in 2017. With >300 mAbs in clinical trials and many more under pre-clinical development, the market size is expected to grow further. Although a palette of powerful technologies (e.g. hybridoma, single B-cell PCR, in vitro selection) has been developed in this field, the generation of antibodies that bind to many biomedically important molecules still presents a daunting challenge. For example, it is difficult to raise high affinity antibodies binding to hydrophilic and conformationally flexible glycan structures, or antibodies with an inhibitory effect by penetrating a catalysis pocket, or antibodies as agonists to regulate membrane proteins like GPCRs. Our lab aims to discover, engineer, and produce mAbs that are difficult to be generated using current techniques. We develop a set of novel methodologies that rely on combination of combinatorial library construction, structure-aided design, functional rather than binding-based selection, deep DNA sequencing, transfection and display techniques, etc. These methodologies provide a powerful means for the generation of highly potent antibodies displaying desired biological activities relevant to disease diagnosis and treatment. Current collaborators: Dr. Huiwang Ai (U Virginia), Dr. Vincent Dive (CEA, France), Dr. Rong Hai (UCR), Dr. Ru-Rong Ji (Duke), Dr. Markus Kalkum (City of Hope), Dr. Wenbo Ma (UCR), Dr. Ameae Walker (UCR). Funding: NIH, NSF, California Breast Cancer Research Program, UC Caner, UCR-City of Hope Initiative Grant.