POSTECH, Ph. D.
We are proud of our contribution to one of the most important advances in the study of antibody therapeutics since the discovery of monoclonal antibodies a quarter century ago: the conception, design and creation of combinatorial antibody libraries, currently the most widely used of all libraries in the field of biochemistry and which enabled a broadening of the scope of action of the immune system. The advances in the use of antibodies as therapeutic tools have provided new ways of preventing and treating immune disorders, degenerative diseases and different types of tumors. In many cases, the use of antibodies has alleviated the suffering of patients and has halted the progression of the disease. Our research has managed to create a synthetic immune system in the test tube, as well as demonstrating its preventive and therapeutic potential due to exceeding the natural antibody repertoire the human body can generate.
Evolving New Technologies for Antibody Selection
1. Unbiased functional antibody selection
Conventional method to select antibody is based on its binding property. Because the antibody affinity does not always correlates with its activity, each binding antibody should be tested in a secondary functional screen. To improve the complexity of the conventional antibody selection, we devised a direct selection method for functional antibody in eukaryotic cells. When combinatorial antibody libraries are rendered infectious for eukaryotic cells, the integrated antibody genotype and cellular phenotype, become permanently linked and each cell becomes a selection system unto itself. In addition, this approach enabled us to select functional agonist antibody against unknown targets
2. Agonist antibody selection
To improve the adaptability of method to diverse phenotypic screening, we also developed a specialized “Near Neighbor” approach in which the entire antibody library and its target receptor are co-integrated into the plasma membranes of a population of reporter cells. This format favors unusual interactions between receptors and their protein ligands and ensures that the antibody acts in an autocrine manner on the cells that produces. This system should be generalizable to any pathway where its activation can be linked to production of a selectable phenotype.
Development of Therapeutic Antibodies
1. Antibody-induced cancer cell differentiation
Recently, we reported that agonist antibody of Thrombopoietin receptor may induce differentiation of killer cells from acute myeloid cells (AML). Intriguingly, the antibody-induced killer cells showed cytotoxic activity against cancer cells. In this study, we suggested the possibility of agonist antibodies to change the differentiation state of cancer cells into those that attack and kill other members of the malignant clone from whence they originate. In the future, we would like to expand this project to develop efficient strategies to reduce the recurrence of AML.
2. Anti-Tspan12 antibody for vaso-proliferative retinopathy
In addition to blood cancer, we are also interested in eye disease such as retinopathy. Recently, we developed an anti-Tspan12 antibody suppressing the Tspan12/B-catenin signaling pathway. Anti-Tspan12 antibody showed a strong anti-angiogenic effect on both in vitro and in vivo. In the future, we would like to conjugate endothelial-specific anti-Tspan12 antibody with strong anti-angiogenic cytokine, Interferon r to propose potent, endothelial cell specific therapeutic strategy for vaso-proliferative retinopathies.