Grant: CIHR Fellowship

Monoclonal antibodies are counterparts of the natural antibodies that protect us against disease. Monoclonal antibodies have transformed medical research and are the fastest growing class of drugs, providing breakthrough treatments for arthritis or cancer. Current techniques for the generation of monoclonal antibodies are expensive and result in antibodies that are suboptimal and induce immune reactions in a significant proportion of patients. Supervised by Dr Schrader, an expert in monoclonal antibodies, I will work with an engineering student to exploit advances made by a physicist, Dr Hansen, in the fabrication of microfluidic devices the size of a postage stamp that I can fill with hundreds of isolated single antibody-secreting cells, each in its own compartment. I will develop efficient methods to purify individual cells from blood samples from immunized patients or rabbits, each one of which is likely to be making an antibody against a particular target. Using the chip I will simultaneously analyze the quality of the antibodies and copy together the genes that encode each one of these antibodies. Using standard methods, we can use these genes to produce unlimited quantities of the best antibodies. I will make two sets of antibodies, human monoclonal antibodies useful in treating or preventing avian influenza virus, and rabbit monoclonal antibodies targeting M-Ras, a protein involved in human cancer that will be useful in predicting patient survival and optimizing treatments. The techniques I will develop will solve an important practical and theoretical question, about the tightness with which natural antibodies can bind and will enable us to copy truly human antibodies that have been generated in a human and should be well-tolerated in patients. The realization of high-throughput methods for the rapid and inexpensive production of high-quality monoclonal antibodies will also have far-reaching impact in accelerating basic and applied medical research.