Our research area is in between clinical and basic science, involving immunology, microbiology, and oncology. Persistent viral infection causes various diseases by inducing immunodeficiency, malignancy, autoimmunity, and inflammation. Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), and Human T-cell leukemia virus type-I (HTLV-I) causes adult T-cell leukemia (ATL) and various chronic inflammatory autoimmune-like diseases. To understand mechanisms of these diseases, investigation on host immunity is indispensable. Immune responses are usually protective but sometimes harmful for the host, and are important determinants for disease manifestation. The goal of our research is elucidation of the role of host immunity in the diseases in order to develop effective immunotherapy. We also investigate intracellular mechanisms of viral replication to target direct molecules for therapy.
1. Analysis of immunological risks for ATL development in HTLV-I-carriers.
2. Development of anti-tumor vaccine against ATL.
3. Immunological and molecular mechanism of HTLV-1-induced leukemogenesis.
4. Molecular mechanism of HIV replication especially related to HIV-1 integrase.
5. Experiments based on gene therapy to suppress HIV-1 replication.
① Development and clinical study of anti-ATL vaccine therapy with Tax peptide-pulsed autologous dendritic cells.
Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-I (HTLV-I)-infected T-cell malignancy with poor prognosis. We developed a novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti-ATL effects, and conducted a pilot study to investigate its safety and efficacy in collaboration of Tokyo Medical and Dental University, National Kyushu Cancer Center, and Kyushu University. The vaccine consists of autologous dendritic cells pulsed with Tax peptides corresponding to the CTL epitopes. Two of three patients administered with the vaccine achieved partial and complete remission without severe side effects. The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC vaccine is a safe and promising immunotherapy for ATL（Suehiro, Y., Hasegawa, A., et al. Brit J Haematol. 169: 356-367, 2015. doi: 10.1111/bjh.13302）.
②Involvement of innate immune response in HTLV-1 pathogenesis.
The constitutive activation of NFκB plays an important role in leukemogenesis of adult T-cell leukemia/lymphoma (ATL) caused by human T-cell leukemia virus type-1 (HTLV-1). Although HTLV-1 Tax is known to activate NFκB, ATL cells exhibit NFκB activities even in the absence of Tax expression, the mechanism of which has been a long-puzzling question. We demonstrate that both double-stranded RNA-dependent protein kinase (PKR) and anti-sense HTLV-1 transcripts are involved in the constitutive NFκB activation in Tax-negative ATL cells. Our findings elucidate a novel Tax-independent mechanism of NFκB activation underlying HTLV-1 leukemogenesis in which host antiviral responses are involved (Kinpara, S., et al. Leukemia, 29:1425-1444, 2015. doi: 10.1038/leu.2015.1).
① For under graduate students of the medical school, we participate in education of basic immunology I, and II, the project semester, and the preclinical clarkship.
② Graduate students are trained for basic skills in the field of immunology and virology to handle biohazard materials. We provide the opportunity to research for mechanisms of the retro-virus-mediated diseases and development of immunological therapeutics. All the stuffs and students participate in maintenance of the laboratory and periodical seminars to discuss about their own studies and keep up with the latest knowledge and information in the area.
Lectures & Courses
We always think of the clinical significance of the results of basic research. We try to find an effective therapy by approaching from basic research to understand the disease mechanisms and solve the problem. The disease mechanisms that we study include leukemogenesis, inflammation, immunosuppression, and autoimmunity in persistent virus infection. Through these studies, we contribute to clinical therapies as well as medical sciences.
Clinical Services & Other Works
We held the 5th Annual Meeting of Japanese Society of HTLV-1 Associated Diseases in Tokyo on Aug 31 through Sept 2, 2018.
We developed an anti-ATL immunotherapy (Tax peptide-pulsed dendritic cell vaccine), which is under clinical studies in collaboration with National Kyushu Cancer Center and Kyushu University. We evaluate anti-tumor and anti-virus T-cell responses in HTLV-1-infected patients with or without various therapies including the immunotherapy and hematopoietic stem cell transplantation, in response to requests from clinical doctors.