Development of Aptamers Against CD20 for treating B-Cell Non-Hodgkin Lymphoma

B-cell non-Hodgkin lymphomas (NHL) are the most prevalent type of NHL and are often resistant to chemotherapy regimens. Rituximab, a monoclonal antibody used to treat B-cell NHL, binds to CD20, a target overexpressed in 90% of patients. In general, monoclonal therapies are expensive and have drawbacks.  Nucleic acid aptamer technologies could be a cheaper and easier approach.  I am working with Andrew Ellington on the “People’s Aptamer Project” to produce aptamers against biomedically relevant and therapeutically validated targets, creating an affordable treatment option for developing nations.  The Project is also in collaboration with Altermune Technologies, brainchild of Kary Mullis, to developed the aptamers into immunogen based therapies by conjugating the aptamer binding agents to sugar immunogens.  The “alphamer” drugs recruit an immune killing response through both antibody dependent cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) towards an aptamer bound cell thus eliciting the desired therapy. 

CD20 aptamers have been generated in vitro and in vivo starting with a random library of nucleic acids followed by systematic evolution of ligand by exponential enrichment (SELEX) against both purified CD20 and cell lines expressing CD20.  Selection techniques such as real time PCR, whole cell SELEX, and high throughput sequencing will be presented along with binding and activity data.