Science and Technology Platform Program for Advanced Biological Medicine


Development of cancer-specific antibodies for refractory cancers and its clinical application

<Project Leader> Yukinari Kato

New Industry Creation Hatchery Center, Tohoku University / Department of Antibody Drug Development, Tohoku University Graduate School of Medicine

Yukinari Kato

In our project, we aim to develop cancer specific monoclonal antibodies (mAbs) using our original technologies, the CasMab method. We will immediately transfer the developed mAbs to pharmaceutical companies. Antibody drugs have been used for cancer therapy; however, the toxicity against normal cells are always worried when non-cancer specific mAbs are used in clinical studies. Because cancer-specific antigens are known to be limited, it might be difficult to develop mAbs for novel molecular targets. For the conventional production of mAbs, synthetic peptides or recombinant proteins using E. coli and mammalian cells such as CHO or HEK-293T. In this study, we will use cancer cell lines, which could produce cancer-specific glycans. We plan to combine the CasMab method with GpMab method to develop anti-glycopeptide mAbs and cell-based immunization and screening (CBIS) method to produce mAbs using target-overexpressed cell lines. Recently, the antibody drug conjugate (ADC), the radioimmunotherapy (RIT), and the chimeric antigen receptor T (CAR-T) therapy have been developed for novel modalities of antibody therapies and immunotherapies. We also plan to utilize these technologies for our original cancer-specific mAbs. The final goal of this project is the development of cancer-specific antibody drugs or immunotherapies without side effects for refractory cancers such as mesotheliomas or brain tumors.

Figure 1 Figure 1: Development of cancer specific mAb (CasMab). Both cancer cells and normal cells possess the same proteins and glycans. Cancer-specific mAbs (CasMabs) can detect the structural change of glycoproteins, which are expressed in cancer cells.
Figure 2 Figure 2: Determination of cancer-specificity using flow cytometry (FCM) and immunohistochemical analysis (IHC). Both CasMab (LpMab-23) and non-CasMab (LpMab-17) react with cancer cells in flow cytometry, but CasMab does not react with normal cells in FCM (left). Likewise, CasMab shows cancer-specificity in IHC (upper right). Epitope mapping of CasMab is shown (lower right).
Figure 3 Figure 3: CO2 Incubators for antibody production.
Figure 4 Figure 4: Flow cytometers for antibody screening.


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