“As a research lab, we have been involved in basic discovery and translational science, and making the transition to commercial use is currently one of the major gaps in the field,” said Mitchell Ho, Ph.D., chief of the antibody therapy section at the National Cancer Institute. Dr. Ho and colleagues are focused on the development of therapeutic antibodies for several types of malignant tumors. This process relies on phage display in E. coli, followed by the transition to mammalian expression systems to generate the constructs of interest.
“In recent years, we became particularly interested in single-domain antibodies,” said Dr. Ho. The lack of the immunoglobulin light chain provides single-domain antibodies with unique functional characteristics because the heavy chains are able to better recognize unique and novel hidden epitopes that would not be accessible for whole immunoglobulin G molecules.
Research efforts in Dr. Ho’s laboratory led to the synthesis of a human heavy-chain, variable-domain antibody, HN3, against glypican-3, which promises to provide a new therapeutic approach for liver cancer. Additionally, Dr. Ho and colleagues recently reported the synthesis of SD1, the first human single-domain antibody that targets tumors expressing mesothelin, a plasma membrane differentiation antigen. This could improve the therapeutic prospects of patients with mesothelin-expressing tumors, which include mesothelioma, ovarian cancer, and pancreatic and lung adenocarcinoma.
Current efforts in Dr. Ho’s laboratory are focused on synthesizing immunocytokines, which consist of antibodies fused to cytokines and are promising therapeutic candidates. “For some of these immunocytokines, expression in mammalian systems is too low, but baculovirus expression systems in insect cells work well, and we showed that the products, in addition to being expressed at high levels, are soluble and active,” said Dr. Ho.