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  1. Article ; Online: Intratumoral cancer immunotherapy exploiting anti-viral immunity.

    Kadowaki, Norimitsu

    Journal of clinical and experimental hematopathology : JCEH

    2021  Volume 62, Issue 1, Page(s) 1–8

    Abstract: After a long period of endeavor, immunotherapy has become the mainstream of cancer therapies. This success is mostly ascribed to immune checkpoint blockade, chimeric antigen receptor-transduced T cell therapies, and bispecific antibodies. However, these ... ...

    Abstract After a long period of endeavor, immunotherapy has become the mainstream of cancer therapies. This success is mostly ascribed to immune checkpoint blockade, chimeric antigen receptor-transduced T cell therapies, and bispecific antibodies. However, these methods have been effective or applicable to only a limited proportion of patients so far. Thus, further development of broadly applicable and effective immunotherapies is eagerly anticipated. Given that innate immunity is key to the induction of robust adaptive immunity and that the immunosuppressive tumor microenvironment is a major hurdle to overcome, intratumoral immunotherapy in which delivery of immunostimulatory microbial agents to the tumor site triggers innate immunity in situ is a rational strategy. There has been a plethora of preclinical and clinical trials conducted involving the delivery of either mimetics of viral nucleic acids or oncolytic viruses intratumorally to trigger innate immunity via various nucleic acid sensors in the tumor site. Many of these have shown significant antitumor effects in mice, particularly in combination with immune checkpoint blockade. Oncolytic herpes simplex virus type 1 has been approved for the treatment of advanced melanoma in the United States and Europe and of glioblastoma in Japan. Whereas direct intratumoral administration has mainly been chosen as a delivery route, several promising compounds amenable to systemic administration have been developed. Intratumoral delivery of immunostimulatory agents will become an important option for cancer immunotherapy as an off-the-shelf, broadly applicable, and rational strategy that exploits the physiology of immunity, namely anti-microbial immunity.
    MeSH term(s) Animals ; Antiviral Agents ; Humans ; Immunotherapy ; Mice ; Neoplasms/therapy ; Oncolytic Viruses ; Tumor Microenvironment
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2021-10-26
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2395568-5
    ISSN 1880-9952 ; 1880-9952
    ISSN (online) 1880-9952
    ISSN 1880-9952
    DOI 10.3960/jslrt.21023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Guest editorial: advances in immunotherapy for hematological malignancies.

    Kadowaki, Norimitsu

    International journal of hematology

    2018  Volume 107, Issue 3, Page(s) 260–261

    MeSH term(s) Hematologic Neoplasms/immunology ; Hematologic Neoplasms/pathology ; Hematologic Neoplasms/therapy ; Humans ; Immunotherapy/methods ; Immunotherapy/trends
    Language English
    Publishing date 2018-02-09
    Publishing country Japan
    Document type Editorial
    ZDB-ID 1076875-0
    ISSN 1865-3774 ; 0917-1258 ; 0925-5710
    ISSN (online) 1865-3774
    ISSN 0917-1258 ; 0925-5710
    DOI 10.1007/s12185-018-2420-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: [Cancer therapy using bispecific antibodies].

    Kadowaki, Norimitsu

    Rinsho ketsueki] The Japanese journal of clinical hematology

    2018  Volume 59, Issue 10, Page(s) 1942–1947

    Abstract: Bispecific antibodies comprise two antigen-binding sites that recognize different antigens or epitopes. Blinatumomab, a bispecific T-cell engager (BiTE) that lacks the Fc portion, recognizes CD19 on B tumor cells and CD3 on T cells and induces the T cell- ...

    Abstract Bispecific antibodies comprise two antigen-binding sites that recognize different antigens or epitopes. Blinatumomab, a bispecific T-cell engager (BiTE) that lacks the Fc portion, recognizes CD19 on B tumor cells and CD3 on T cells and induces the T cell-mediated killing of the B tumor cells. The Food and Drug Administration has approved the use of blinatumomab for the treatment of precursor B-cell acute lymphoblastic leukemia (ALL) with minimal residual disease and relapsed/refractory ALL. Various bispecific antibodies have been developed, including BiTEs that target surface molecules on myeloma cells or intracellular antigens presented on the major histocompatibility complex and Fc portion-containing bispecific antibodies that have a potent T cell-activating capacity and a long half-life. These efforts could lead to the development of potent, off-the-shelf bispecific antibodies for the treatment of a broad array of hematological malignancies.
    MeSH term(s) Antibodies, Bispecific/therapeutic use ; Antigens, CD19 ; Antineoplastic Agents/therapeutic use ; Hematologic Neoplasms/therapy ; Humans ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy ; T-Lymphocytes
    Chemical Substances Antibodies, Bispecific ; Antigens, CD19 ; Antineoplastic Agents
    Language Japanese
    Publishing date 2018-10-10
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 390900-1
    ISSN 0485-1439
    ISSN 0485-1439
    DOI 10.11406/rinketsu.59.1942
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Hairy cell leukaemia with an IGH-BRAF fusion gene.

    Matsumoto, Kensuke / Kakazu, Naoki / Imataki, Osamu / Kondo, Akihiro / Kanaji, Nobuhiro / Kadowaki, Norimitsu

    British journal of haematology

    2023  Volume 202, Issue 6, Page(s) e67–e70

    MeSH term(s) Humans ; Leukemia, Hairy Cell/genetics ; Proto-Oncogene Proteins B-raf/genetics
    Chemical Substances Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; BRAF protein, human (EC 2.7.11.1)
    Language English
    Publishing date 2023-07-11
    Publishing country England
    Document type Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Application of PD-L1 blockade in refractory histiocytic sarcoma: A case report.

    Imataki, Osamu / Uemura, Makiko / Fujita, Haruyuki / Kadowaki, Norimitsu

    Molecular and clinical oncology

    2022  Volume 17, Issue 3, Page(s) 136

    Abstract: Histiocytic sarcoma (HS) is a rare hematological malignancy, which exhibits morphological and immunophenotypic features of histiocytes. A standard therapy for HS has not yet been established due to its rareness; therefore, disease control is not always ... ...

    Abstract Histiocytic sarcoma (HS) is a rare hematological malignancy, which exhibits morphological and immunophenotypic features of histiocytes. A standard therapy for HS has not yet been established due to its rareness; therefore, disease control is not always possible. A multimodal treatment strategy has been suggested for HS. The present study reported on a case of a 43-year-old female patient who complained of left femoral pain, which was caused by left femoral bone mass. A biopsy of their left femoral bone tumor revealed that the patient had HS. Their sarcoma was localized in the femoral bone and was not considered to be curable, due to local infiltration of the bone tumor beyond the periosteum. The patient then underwent two types of HS-specific chemotherapy; however, both regimens were ineffective. As a result, they underwent radiation therapy at the sites of progressive disease. Because the HS cells of the patient expressed PD-L1, they were treated with nivolumab (240 mg/body, biweekly) for residual diseases in the right occipital bone, multiple lung nodules, intrapelvic right lymph node and primary site. Nivolumab treatment resulted in a complete response at all sites, with the exception of the primary site, which was confirmed by
    Language English
    Publishing date 2022-07-15
    Publishing country England
    Document type Case Reports
    ZDB-ID 2796865-0
    ISSN 2049-9469 ; 2049-9450
    ISSN (online) 2049-9469
    ISSN 2049-9450
    DOI 10.3892/mco.2022.2569
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: [Combination of Targeted Therapy and Immunotherapy for Cancer].

    Kadowaki, Norimitsu

    Gan to kagaku ryoho. Cancer & chemotherapy

    2015  Volume 42, Issue 9, Page(s) 1046–1049

    Abstract: Targeted therapies and immunotherapies attack tumor cells through different mechanisms. In addition, these therapies exhibit quick and delayed effects, respectively, and therefore, these therapies are complementary. Furthermore, targeted therapies may ... ...

    Abstract Targeted therapies and immunotherapies attack tumor cells through different mechanisms. In addition, these therapies exhibit quick and delayed effects, respectively, and therefore, these therapies are complementary. Furthermore, targeted therapies may enhance the function of immune cells, and therefore, both the therapies are expected to have a synergistic effect. Antitumor immune responses comprise several steps including dendritic cell activation, T cell activation, and dampening tumor-induced immunosuppression; targeted drugs that work at each step have been reported. Clinical trials of rational combinations of both therapies, while avoiding severe adverse events, will greatly advance cancer treatments in the near future.
    MeSH term(s) Cancer Vaccines/immunology ; Dendritic Cells/immunology ; Humans ; Immunotherapy ; Lymphocyte Activation ; Neoplasms/immunology ; Neoplasms/therapy ; T-Lymphocytes/immunology
    Chemical Substances Cancer Vaccines
    Language Japanese
    Publishing date 2015-09
    Publishing country Japan
    Document type English Abstract ; Journal Article
    ZDB-ID 604842-0
    ISSN 0385-0684
    ISSN 0385-0684
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Guest editorial: Immunotherapy for hematological malignancies: the quest to overcome tolerogenic drive.

    Kadowaki, Norimitsu

    International journal of hematology

    2014  Volume 99, Issue 2, Page(s) 105–106

    MeSH term(s) Hematologic Neoplasms/immunology ; Hematologic Neoplasms/therapy ; Humans ; Immune Tolerance ; Immunotherapy ; Translational Medical Research
    Language English
    Publishing date 2014-01-07
    Publishing country Japan
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 1076875-0
    ISSN 1865-3774 ; 0917-1258 ; 0925-5710
    ISSN (online) 1865-3774
    ISSN 0917-1258 ; 0925-5710
    DOI 10.1007/s12185-013-1498-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Clinical effects of tacrolimus blood concentrations early after allogeneic hematopoietic stem cell transplantation.

    Kubo, Hiroyuki / Imataki, Osamu / Fukumoto, Tetsuya / Ishida, Tomoya / Kubo, Yukiko Hamasaki / Yoshida, Shunsuke / Uemura, Makiko / Fujita, Haruyuki / Kadowaki, Norimitsu

    Cytotherapy

    2024  

    Abstract: Background aims: Tacrolimus (TAC) plus short-term methotrexate (stMTX) is used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). TAC blood concentrations are frequently adjusted to ... ...

    Abstract Background aims: Tacrolimus (TAC) plus short-term methotrexate (stMTX) is used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). TAC blood concentrations are frequently adjusted to enhance the graft-versus-leukemia/lymphoma effect or attenuate severe GVHD. Limited information is available on the clinical impact of these adjustments and the optimal time to perform them in order to achieve good clinical outcomes.
    Methods: We retrospectively analyzed 211 patients who underwent allo-HSCT at our institutes.
    Results: Higher TAC concentrations in week 3 correlated with a significantly higher cumulative incidence of relapse (CIR) (P = 0.03) and lower nonrelapse mortality (P = 0.04). The clinical impact of high TAC concentrations in week 3 on CIR was detected in the refined disease risk index: low/intermediate (P = 0.04) and high (P < 0.01), and conditioning regimens other than cyclophosphamide/total body irradiation and busulfan/cyclophosphamide (P = 0.07). Higher TAC concentrations in week 1 correlated with a lower grade 2-4 acute GVHD rate (P = 0.01). Higher TAC concentrations in weeks 2 and 3 correlated with slightly lower (P = 0.05) and significantly lower (P = 0.02) grade 3-4 acute GVHD rates, respectively. Higher TAC concentrations in weeks 1 and 3 were beneficial for severe acute GVHD in patients with a human leukocyte antigen-matched donor (P = 0.03 and P < 0.01, respectively), not treated with anti-thymocyte globulin (P = 0.02 and P = 0.02, respectively), and receiving three stMTX doses (P = 0.03 and P = 0.02, respectively).
    Conclusions: The clinical impact of TAC concentrations varied according to patient characteristics, including disease malignancy, conditioning regimens, donor sources, and GVHD prophylaxis. These results suggest that TAC management needs to be based on patient profiles.
    Language English
    Publishing date 2024-03-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.1016/j.jcyt.2024.02.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Repeated spontaneous remission of acute myeloid leukemia in response to various infections: a case report.

    Imataki, Osamu / Ishida, Tomoya / Kida, Jun-Ichiro / Uemura, Makiko / Fujita, Haruyuki / Kadowaki, Norimitsu

    BMC infectious diseases

    2023  Volume 23, Issue 1, Page(s) 215

    Abstract: Background: Acute myeloid leukemia (AML) is a progressive hematological malignancy that can be fatal when left untreated. However, spontaneous remission is rarely observed in the presence of infectious diseases.: Case presentation: We treated an 80- ... ...

    Abstract Background: Acute myeloid leukemia (AML) is a progressive hematological malignancy that can be fatal when left untreated. However, spontaneous remission is rarely observed in the presence of infectious diseases.
    Case presentation: We treated an 80-year-old woman with AML who spontaneously underwent remission after infections. Spontaneous remission was observed after each of three independent clinical infections caused by different pathogens-nontuberculous Mycobacterium infection, pulmonary aspergillosis, and Escherichia coli bacteremia. All infections were treated promptly with antimicrobials. Mycobacterium avium infection was treated with azithromycin, rifampin, and ethambutol. Pulmonary aspergillosis was treated with itraconazole followed by voriconazole. E. coli infection was treated with meropenem. During each infectious episode, leukemic cells disappeared from the patient's peripheral blood and pancytopenia improved without routine blood transfusion. These clinical effects lasted for several months. The patient has survived for > 2 years beyond the median survival time of end-stage AML. Thus, this case represents an immunological antileukemic effect of systemic infections.
    Conclusions: We have discussed a common mechanism of spontaneous remission of AML without chemotherapy, clinically exhibited by infection immunology. We believe that infections exert a limited immunological effect against AML, which may prolong survival among elderly individuals with AML.
    MeSH term(s) Female ; Humans ; Aged ; Aged, 80 and over ; Remission, Spontaneous ; Escherichia coli ; Leukemia, Myeloid, Acute/complications ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/pathology ; Pulmonary Aspergillosis ; Voriconazole/therapeutic use ; Escherichia coli Infections
    Chemical Substances Voriconazole (JFU09I87TR)
    Language English
    Publishing date 2023-04-06
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2041550-3
    ISSN 1471-2334 ; 1471-2334
    ISSN (online) 1471-2334
    ISSN 1471-2334
    DOI 10.1186/s12879-023-08108-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: [Cell therapy].

    Kadowaki, Norimitsu

    Nihon rinsho. Japanese journal of clinical medicine

    2012  Volume 70 Suppl 2, Page(s) 274–278

    MeSH term(s) Cell Transplantation/methods ; Hematologic Neoplasms/therapy ; Humans
    Language Japanese
    Publishing date 2012-04
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 390903-7
    ISSN 0047-1852
    ISSN 0047-1852
    Database MEDical Literature Analysis and Retrieval System OnLINE

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