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New Technologies for Therapeutic Antibody

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.

2. Agonist antibody selection


To improve the adaptability of method to diverse phenotype 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 membrane 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.

Molecule

Research

Protein Engineering Lab

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 enkaryotic cells, the integrated antibody genotype and cellular phenotype become permanently linked and each cell becomes a selection system unto itself.

2. Agonist antibody selection


To improve the adaptability of method to diverse phenotype 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 membrane 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.

3. Development of Therapeutic antibodies

Recently, we reported that agonist antibody of Thrombopoietin receptor may induce differentiation of killer cells from acute myeloid leukemia(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 expend this project to develop efficient strategies to reduce the recurrence of AML.

In addition to leukemia, 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 to propose potent, endothelial cell specific therapeutic strategy for vaso-proliferative retinopathies.