③COVID-19 by anti-TMPRSS2①Hepatitis by anti-NTCPThe Drug Discovery Antibody Platform Unit (Ab Platform) is one of nine 49SARS-CoV2anti-CRTAManti-NTCPanti-TMPRSS2②EAE by anti-CRTAMDrug 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.1) We have developed a mAb against a human receptor of hepatitis B virus (HBV), NTCP, in the last few years. Because HBV binds via the preS1-domain of the viral L protein to the apical sodium-acid dependent bile acid transporter (NTCP), NTCP could be a key target for the development of anti-HBV agents. Indeed, the established mAb inhibits the entry of HBV into human liver cells in vitro and further inhibits in vivo infection in a system using human-liver chimeric mice. Human chimeric NTCP mAbs are being developed for further clinical applications. 2) We also established mAbs against CRTAM (Cytotoxic And Regulatory T Cell Molecule). CRTAM is critical for the development/function of CD4+ cytotoxic T cells (CTL), which are thought to be critical for the induction of IBD, inflammatory bowel diseases, as well as late-phase induc-tion of EAE, experimental autoimmune encephalomyelitis. Several established mAbs were tested for their ability to modulate these diseases in mice. Indeed, preliminary results showed a significant inhibition of late-phase of EAE induc-tion by administration of a CRTAM mAb, suggesting potential therapeutic use of mAbs. 3) More recently, we have tried to establish 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. However these small molecules also have some side-effects, therefore the mAbs against TMPRSS2 may have more specific inhibitory activity and possibly modulate COVID-19 (Figure). Further-more, we are also trying to generate mAbs specific for various cancers.Figure: Development of monoclonal antibodies for therapeutic use targeting various diseasesMonoclonal Abs have been developed to modulate/in-hibit the diseases of viral hepatitis ①, SARS-CoV2 infec-tion ②, Multiple sclerosis mouse model (experimental autoimmune encephalomyelitis) ③, and cancer.Recent Major PublicationsSugimoto-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)Nakano T, Ochiai S, Suzuki S, Yamaide F, Morita Y, Inoue Y, Arima T, Kojima H, Suzuki H, Nagai K, Morishita N, Hata A, Shozu M, Suzuki Y, Taniguchi M, Takemori T, Kohno Y, Shimojo N. Breastfeeding promotes egg white sensitiza-tion in early infancy. Pediatr Allergy Immunol 31, 315-318 (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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