We have worked to harness the innate and adaptive immune systems, 54resulting in the induction of immunological memory against cancer. To this end, we have performed both basic immunology and translational stud-ies. We have focused on the role of dendritic cells (DCs) in vivo, and in par-ticular on two ongoing projects in cancer immunology and infectious disease in the current year. First, we developed an immunotherapeutic strategy using tumor-derived neo-antigens. We identified three H2-Kb-restricted, somatically-mutated epitopes as immunogenic neoantigens and showed their efficacy using DCs (Figure). Second, we extended the artificial adjuvant vector cells (aAVC) system to COVID-19. We have been developing SARS-CoV-2-derived antigen-expressing aAVC (aAVC-Cov-2). We will examine a proof of concept in anti-viral cytotoxic T cell induction as well as anti-SARS-CoV-2 Ab production in vaccinated animals. We have been working on two translational research projects. We finished the phase II NKT cell therapy for NSCLC patients trial in collaboration with the National Hospital Organization (NHO) and found that the NKT and NK cell responses in treated patients were stronger than those in untreated patients. In another study, we have established an investigator-initiat-ed phase I clinical trial for relapsed and refractory acute myelogenous leukemia using aAVC-expressing Wilms Tumor (WT1) antigen (aAVC-WT1) therapy. This trial has been conducted at the Department of Hematology/Oncology, the Institute of Medical Science, the University of Tokyo in a collaboration started in 2017. We have been engaged in the immunological analyses of the aAVC-WT1 treated patients. We are now preparing for the phase II clinical trial.Figure: Therapeutic efficacy of DCs pulsed with multiple neoantigen epitopesWe screened neoantigen epitopes in murine colorectal cancer MC38 cells and identified three H2-Kb restricted, somatically-mutated immunogenic neoantigens. MC38 cells were administered to mice s.c. One week later, the mice were treated with neoantigen-pulsed DCs twice at a one-week interval. Immunotherapy with neoantigen peptide-pulsed DCs resulted in decreased tumor growth in the MC38 tumor-bearing mice.Recent Major PublicationsOkada M, Shimizu K, Iyoda T, Ueda S, Shinga, Mochizuki Y, Watanabe T, Ohara O, Fujii S. PD-11 expression affects neoantigen presentation. iScience 23, 101238 (2020)Seo W, Shimizu K, Kojo S, Okeke A, Kohwi-Shigematsu T, Fujii S, Taniuchi I. Runx-mediated regulation of CCL5 via antagonizing two enhancers influences immune cell function and anti-tumor immunity. Nat Commun. 11, 1562 (2020)Shimizu K, Iyoda T, Yamasaki S, Kadowaki N, Tojo A, Fujii S. NK and NKT Cell-Mediated Immune Surveillance Against Hematological Malignancies. Cancers (Basel) 12, 817 (2020)Invited presentationsFujii S. “Development of artificial adjuvant vector cells (aAVC) inducing both innate and adaptive immunity” The 41st Annual Scientific Meeting of the Japanese Soci-ety of Clinical Pharmacology and Therapeutics (Fukuoka, Japan) December 2020Fujii S. “Immune cells in tumor microenvironment” The 82nd Annual Meeting of the Japanese Society of Hema-tology (Japan/Online) October 2020Fujii S. “Anti-cancer therapeutic cellular drug, artificial adjuvant vector cells by targeting in vivo dendritic cells” The 79th Annual Meeting of the Japanese Cancer As-sociation (Hiroshima, Japan) October 2020Fujii S. “Development of anti-cancer therapeutic cellular drug as in vivo DC targeting therapy artificial adjuvant vector cells (aAVC)” The 12th Annual Meeting of Japa-nese Scoiety of Immunotherapy for Hematological Disorders (Osaka, Japan) September 2020Fujii S. “Tumor-Immune network and recent progress in Cancer Immunotherapy” The 106th General Meeting of the Japanese Society of Gastroenterology (Hiroshima, Japan) August 2020Laboratory for ImmunotherapyTeam Leader: Shin-ichiro Fujii
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