ABCThe Drug Discovery Antibody Platform Unit (Ab Platform) is one of nine 53N6HB426-20 Abs and preS1 concentration (nM)NTCPNTECL1HB426ECL2ECL3ECL4HBVDrug Discovery Basic Units in the Drug Discovery and Medical Technol-ogy Platform (DMP). DMP develops innovative new pharmaceuticals to trans-fer the basic research performed at the institute to the clinics. Particularly, the Ab Platform creates new monoclonal Abs (mAb) for therapeutic purposes of preventing/modulating various diseases.During the last few years, we have developed and analyzed a mAb against a human hepatitis B virus (HBV) receptor, NTCP (sodium-taurocholate co-transporting polypeptide). Because the preS1-domain of HBV binds to NTCP, it could be a key target for the development of HBV blocking agents. Indeed, the established mAb inhibits the entry of HBV into human liver cells in vitro and inhibits in vivo infection in a system using human-liver chimeric mice. Currently available inhibitors of NTCP binding of HBV have the unwanted side effect of also blocking bile acid import, however, this mAb does not. Therefore, the mAb becomes an ideal specific inhibitor of HBV infection without side effects. Now humanized NTCP mAbs are being developed for clinical applica-tions (Figure and publication).We also established mAbs against CRTAM (Cytotoxic and Regulatory T Cell Molecule). CRTAM is critical for the development/function of CD4+ cyto-toxic T cells (CTL), which are thought to be critical for late-phase induction of EAE, experimental autoimmune encephalomyelitis. Indeed, preliminary results showed a significant inhibition of late phase of EAE induction by administra-tion of a CRTAM mAb, suggesting its potential therapeutic use.More recently, we have established mAbs against human TMPRSS2 for the purpose of inhibiting infection with SARS-CoV2. TMPRSS2 is critical for viral entry and small molecule inhibitors of TMPRSS2 have been shown to inhibit SARS-CoV2 infection, although these compounds also have side effects and instability. Therefore, mAbs against TMPRSS2 may have a more specific inhibi-tory function and modulate COVID-19. Indeed, some mAbs showed strong inhibition of any SARS-CoV2 variants in vitro.Figure: Established anti-NTCP mAb prevents HBV infectionA) Schematic structure of NTCP with the susceptible region (ECL4) for HBV binding and blocking of HBV entry by the anti-NTCP mAb. B) Inhibition of HBV infection of a liver cell line by the anti-NTCP mAb, N6HB426. C) Whereas the anti-NTCP mAb blocks HBV entry, it did not block bile-acid import.Recent Major PublicationsTakemori T, Sugimoto-Ishige A, Nishitsuji H, Futamura Y, Harada M, Kimura-Someya T, Matsumoto T, Honma T, Tanaka M, Yaguchi M, Isono K, Koseki H, Osada H, Miki D, Saito T, Tanaka T, Fukami T, Goto T, Shirouzu M, Shi-motohno K, Chayama K. Establishment of a monoclonal antibody against human NTCP that blocks HBV infection. J Virol 96, e0168621 (2022) doi: 10.1128/JVI.01686-21Sugimoto-Ishige A, Harada M, Tanaka M, Terooatea T, Adachi Y, Takahashi Y, Tanaka T, Burrows PD, Hikida M, Takemori T. Bim establishes the B cell repertoire from early to late in the immune response. Int Immunol 33, 79-90 (2020)Tanaka M, Ishige A, Yaguchi M, Matsumoto T, Shirouzu M, Yokoyama S, Ishikawa F, Kitabayashi I, Takemori T, Ha-rada M. Development of a simple new flow cytometric antibody-dependent cellular cytotoxicity (ADCC) assay with excellent sensitivity. J Immunol Methods 464, 74-86 (2019)Drug Discovery Antibody Platform UnitUnit Leader: Takashi Saito
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