• Cancer Immunology Project

Cancer Immunology Project

Anti-tumor immunity for cancer gene therapy Project

Project Leader TannoPhoto

Project Leader
Hidetaka Tanno

Research Summary

T cells play a critical role in adaptive immunity. They express an enormous repertoire of TCRs on their surfaces. Using these TCRs, T cells recognize antigen-HLA complexes presented by pathogenic cells and eliminate them. Therefore, elucidating the interactions between TCRs and antigen-HLA complexes will be useful for developing new therapeutics and preventive vaccines. For example, cancer-specific TCRs have shown promising results in recent clinical trials. However, it is still difficult to find useful antigen-specific TCRs. In our project, we are developing new technology that can identify TCR-antigen-HLA interactions in a high-throughput manner. By employing this technology, we are comprehensively analyzing cancer patients’ TCR-antigen-HLA repertoires to discover cancer-specific TCRs that can be used for T cell therapies. We will also apply this technology to elucidate the mechanisms of virus infections and autoimmune diseases.

T cells recognize antigen-HLA complexes presented by pathogenic cells via TCR.
There are diverse TCRs in human bodies including cancer-specific TCRs and virus-specific TCRs. Characterizing antigen-specificities of TCRs is necessary for engineered T cell therapy as well as vaccine development. However, it has been difficult to determine the antigen-specificities of TCRs. We are developing new technologies to identify TCR and antigen-HLA interactions at the repertoire level.

Selected Publications

  • M Kuraoka et al. (2022) “Infant Antibody Repertoires during the First Two Years of Influenza Vaccination” mBio.
  • J Li et al. (2021) “Molecular Level Characterization of Circulating Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder” Neurology Neuroimmunology&Neuroinflam mation.
  • H Tanno et al. (2020) “A Facile Technology for the High Throughput Sequencing of the Paired VH:VL and TCRβ:TCRα Repertoires.” Science Advances.
  • H Tanno et al. (2020) “Determinants governing T cell receptor α/β-chain pairing in repertoire formation of identical twins” PNAS.
  • CH Lee et al. (2017) “IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions.” Nature Immunology.
  • JR McDaniel et al. (2016) “Ultra-high-throughput sequencing of the immune receptor repertoire from millions of lymphocytes.” Nature protocols.
  • B Wang et al. (2016) “Discovery of high affinity anti-ricin antibodies by B cell receptor sequencing and by yeast display of combinatorial VH: VL libraries from immunized animals.” mAbs.