・Cancer therapy with iPS-derived NKT cellsThe immune system recognizes tumor cells and can mediate antigen-73・Artificial adjuvant vector cells (SARS-Cov-2)・Therapeutic mAbdrugs for multiple sclerosis・Drug development for atopic dermatitis・Artificial adjuvant vector cells (WT1)・Artificial adjuvant vector cells (HPV)・TMPRSS mAbfor SARS-Cov2・NTCP mAbfor HBV infectionIn collaboration with pharmaceutical companiesIdentification& validation of targetsSeed/Lead identificationLead optimization(Terminated in June)Preclinical developmentClinical developmentPhase ⅡⅡPhase ⅠⅠics, pharmaceuticals and medical technologies by facilitating the transfer of basic research discoveries within the institute. DMP supports all phases of the development of new therapeu-tics, from the discovery of promising targets to the identification of potential lead compounds and the acquisition of intellectual property rights to drugs and technologies that can then be brought to the development phase.DMP established ten Drug Discovery Basic Units, in which the types of studies being performed are organized according to the expertise of each PI. IMS has contributed to this effort by set-ting up two facilities, the Drug Discovery Antibody Platform Unit and the artificial Adjuvant Vector Cell (aAVC) Drug Translational Unit. In 2023, IMS had eight collaborative programs with DMP: Development of aAVC expressing Wilms tumor antigen 1 (WT1), specific tumor rejection under certain conditions, however tumors can often evade the immune network. Understanding the tumor immune microenvironment (TIME) will lead to a variety of approaches designed to initiate or enhance antitumor immunity (Figure). The groups in cancer immunology are investigating the target molecules and cells and developing disease stratification systems and new treatment strategies.Tsunoda’s team (Lab for Medical Science Mathematics) developed two analysis architectures based on their original methodology DeepInsight for transforming omics data to image-like form. Also, they clarified that to-pologically associating domains underlie tissue-specific expression of long intergenic noncoding RNAs (iScience, 26, 106640 (2023).Nakagawa’s team (Lab for Cancer Genomics) performed single-cell RNAseq of immune cells that were extracted from different types of human cancer tissues. They showed some significance of the presence of neutrophils and eosinophils on cancer phenotypes. They also established a machine learning algorithm on immune and genomic data to predict the chemotherapy response of GI cancers.Ishikawa’s team (Lab for Human Disease Models) has extended CAR-T cell development from CD25 to other antigens and also from acute myeloid leukemia to non-AML hematologic malignancies. Through integration of scRNAseq, mass cytometry and in vivo treatment results, they are gaining new insights into how engineered T cells acquire robustness and longevity.Fujii’s group (Lab for Immunotherapy) promoted their aAVC projects for cancer. In a reverse translational study they showed a new finding that antigen-specific stem-like memory NK and CD8+ T cells can be induced by the combination of aAVC plus IL-2. For the aAVC-WT1 (Wilms tumor an-tigen 1) project, they continued a Phase II clinical study as multicenter joint research project. In addition, in Koseki’s group (Lab for Developmental Genetics) an iPS-NKT cell clinical trial for head and neck cancer is ongoing and Phase I clinical research using a combination of iPS-NKT and dendritic cells is ready to start. These translational research projects have been sup-ported by an interaction between IMS and the Drug Discovery and Medical Technology Platforms.human papillomavirus (HPV) or SARS-CoV-2 antigen (aAVC-WT1, -HPV and -CoV-2) for cancer and infectious diseases (Shin-ichiro Fujii), iPS-derived NKT cells for cancer (Haruhiko Koseki), a neutralizing mAb for hepatitis B virus infection (Ka-zuaki Chayama), development of a mAb for TMPRSS to prevent SARS-Cov-2 infection (Kazuhiko Yamamoto), development of a mAb for multiple sclerosis (Takashi Saito), and development of a drug for atopic dermatitis (Tomohiro Miyai). The investigator-initiated Phase II clinical trial of aAVC-WT1 against AML/MDS has finished. In addition, an iPS-NKT cell phase I clinical trial for head and neck cancer is ongoing, and Phase I clinical research using a combination of iPS-NKT and DCs is ready to start. A lead evaluation of the mAb for TMPRSS has been conducted. Seed screening for apoptotic dermatitis drug development is underway.Figure: Our groups work on two strategies by analyzing the TIME. One is for stratification of tumor tissue through an omics analysis of tumor cells and TIME, the other one is for the establishment of new cancer immunotherapies.Figure: Collaboration between IMS and DMP for the development of innovative new biologics, pharmaceuticals and medical technologiesNTCP, HBV host entry receptor sodium taurocholate co-transporting polypeptide; TMPRSS, transmembrane protease, serine.Cancer ImmunologyLinkage to RIKEN Program for Drug Discovery and Medical Technology Platforms (DMP)IMS collaborates with DMP to develop innovative new biolog-
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