A5024388913- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Acute Myeloid Leukemia Research
- Polyomavirus and related diseases
- Immunotherapy and Immune Responses
- Acute Lymphoblastic Leukemia research
- Renal Transplantation Outcomes and Treatments
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Transplantation: Methods and Outcomes
- Mesenchymal stem cell research
- Monoclonal and Polyclonal Antibodies Research
- Chronic Myeloid Leukemia Treatments
- Cancer Immunotherapy and Biomarkers
- Glutathione Transferases and Polymorphisms
- Biosimilars and Bioanalytical Methods
- Viral Infectious Diseases and Gene Expression in Insects
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Chronic Lymphocytic Leukemia Research
- Neutropenia and Cancer Infections
- Parvovirus B19 Infection Studies
- Multiple Myeloma Research and Treatments
Nagoya University
2016-2025
Nagoya University Hospital
2017-2023
Boehringer Ingelheim (Taiwan)
2018
Kyowa Hakko Kirin (Singapore)
2017-2018
Otsuka (Japan)
2018
Kyowa Kirin (Japan)
2017-2018
Ministry of Health Labour and Welfare
2018
Boehringer Ingelheim (Canada)
2017
Fred Hutch Cancer Center
2011-2015
Japanese Red Cross Society, Japan
2010
Abstract The effectiveness of chimeric Ag receptor (CAR)–transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second- and later-generation CARs simultaneously transmit costimulatory signals with CD3ζ upon ligation, but may lead severe adverse effects owing the recognition minimal expression outside target tumor. Currently, threshold density for CAR-T cell lysis further activation, including cytokine production, not yet investigated in detail....
T cells genetically modified with a CD19 chimeric antigen receptor (CD19CAR) are remarkably effective against B-cell malignancies in clinical trials. However, major concerns remain regarding toxicities, such as hypogammaglobulinemia, due to aplasia or severe cytokine release syndrome after overactivation of CAR cells. To resolve these adverse events, we aimed develop an inducible system by using tetracycline regulation that would be activated only the presence doxycycline (Dox). In this...
To investigate an up-to-date alternative donor selection strategy, we compared the transplantation outcomes of 8/8 and 7/8 allele–matched unrelated bone marrow (UBMT) with those umbilical cord blood (UCBT) redefined role UCBT extended analysis. Using Cox competing risk regression analyses, analyzed in adult patients acute lymphoblastic leukemia (ALL) myeloid (AML). A total 2472 first myeloablative transplantations between 2000 2010 were included (8/8 UBMT, 1001; 656; UCBT, 815). For chronic...
Abstract The effectiveness of chimaeric antigen receptor (CAR) T-cell immunotherapies against solid tumours relies on the accumulation, proliferation and persistency T cells at tumour site. Here we show that CD8αβ cytotoxic CAR in can be enhanced by deriving expanding them from a single human induced-pluripotent-stem-cell clone bearing selected for efficient differentiation. We also effector further genetically knocking out diacylglycerol kinase, which inhibits antigen-receptor signalling,...
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative post-remission therapy for adult patients with acute myeloid leukemia (AML) in complete remission (CR). The availability of alternative human leukocyte antigen (HLA)-mismatched donors, such as cord blood and haploidentical related could allow to receive allogeneic HCT who are without an HLA-matched sibling or unrelated donor. use these donors preferable advanced disease due the rapid availability. However,...
Adoptively transferred CD19 chimeric antigen receptor (CAR) T cells have led to impressive clinical outcomes in B cell malignancies. Beyond induction of remission, the persistence CAR-T is required prevent relapse and provide long-term disease control. To improve function persistence, we developed a composite co-stimulatory domain signaling moiety, CD79A/CD40, induce nuclear translocating signal, NF-κB, synergize with other signals function. CD79A/CD40 incorporating CD19CAR-T (CD19.79a.40z)...
CD19 chimeric antigen receptor T (CD19CAR-T) cells have achieved promising outcomes in relapsed/refractory B cell malignancies. However, recurrences occur due to the loss of CAR-T persistence. We developed dual T/B co-stimulatory molecules (CD28 and CD40) enhance intense tumoricidal activity CD19.28.40z promoted pNF-κB pRelB downstream signaling while diminishing NFAT upon exposure. demonstrated greater proliferation, which translated into effective anti-tumor cytotoxicity long-term...
Umbilical cord blood (UCB) transplantation is limited by the low number of hematopoietic stem cells in UCB units, which results a engraftment rate transplant recipients. Here, we measured total nucleated cell count and CD34+, CD3+, CD4+, CD8+, CD14+, CD16+/56+ doses each unit evaluated their influence on other outcomes 146 Multivariate analysis showed significant association between higher incidence successful dose CD34+ CD8+ above median (1.4 × 105 15.7 cells/kg, respectively). Engraftment...
Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and many macrophages is a therapeutic challenge. Here, we characterize involved in report that dexamethasone palmitate (DP), liposteroid, can ameliorate such by inhibiting macrophage functions. We found host-derived could exacerbate mouse model through expression higher levels pro-inflammatory TNF-α IFN-γ, lower anti-inflammatory IL-10 than...
Despite a strong association between acute graft-versus-host disease (GVHD) and cytomegalovirus reactivation (CMVR), the joint effect of GVHD CMVR on nonrelapse mortality (NRM) has not been well studied.We evaluated impact NRM stratified according to development using landmark method. This study included 6078 patients who received their first allogeneic hematopoietic cell transplantation (HCT) with preemptive strategy for 2008 2017.The cumulative incidences grade 2-4 (G24GVHD), by day 100,...
Abstract Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across donor types, we retrospectively analyzed patients with leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 2015 279) or without 6338). Because thymoglobulin only drug approved prophylaxis in Japan since September 2008, included alone present analysis. The survivors’...