Clinical application of activated NK cell therapy

• Project/Area Number: 25461443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Tanaka Junji 東京女子医科大学, 医学部, 教授 (50250452)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: NK細胞 / 細胞療法 / 悪性リンパ腫 / 免疫療法

Outline of Final Research Achievements

We could establish the GMP-grade clinical NK cell expansion system under the condition with OKT3, tacrolimus, dalteparin and cytokines such as IL-2 and IL-15 using peripheral blood mononuclear cells (PBMC) from patients with hematological malignancies such as malignant lymphoma. Expanded NK cell had strong cytolytic activity against K562 human leukemic cell line without pre-sensitization. Using this system, we could planed autologous expanded NK cell therapy clinical trial with rituximab (Phase I/II) against relapse/refractory B cell malignant lymphoma.

Research Products

• [Journal Article] Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the Adult ALL WG of the JSHCT. (2016)
  • Author(s): Nishiwaki S, Imai K, Mizuta S, Kanamori H, Ohashi K, Fukuda T, Onishi Y, Takahashi S, Uchida N, Eto T, Nakamae H, Yujiri T, Mori S, Nagamura-Inoue T, Suzuki R, Atsuta Y, Tanaka J.
  • Journal Title: Bone Marrow Transplantation Volume: 51 Issue: 1 Pages: 43-50
  • DOI: 10.1038/bmt.2015.217
  • Peer Reviewed
• [Journal Article] Influence of differently licensed KIR2DL1-positive natural killercells in transplant recipients with acute leukemia: a Japanese national registry study. (2016)
  • Author(s): Arima N, Nakamura F, Yabe T, Tanaka J, Fuji S, Ohashi K, Fukuda T, Miyamura K, Iwato K, Eto T, Mori T, Kobayashi N, Hoshino T, Kato C, Kanamori H, Nakamae H, Atsuta Y, Morishima Y, Kanda Y.
  • Journal Title: BBMT Volume: 22 Issue: 3 Pages: 423-431
  • DOI: 10.1016/j.bbmt.2015.09.029
  • Peer Reviewed
• [Journal Article] Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study. (2016)
  • Author(s): Muroi K, Miyamura K, Okada M, Yamashita T, Murata M, Ishikawa T, Uike N, Hidaka M, Kobayashi R, Imamura M, Tanaka J, Ohashi K, Taniguchi S, Ikeda T, Eto T, Mori M, Yamaoka M, Ozawa K.
  • Journal Title: Int J Hematol Volume: 103 Issue: 2 Pages: 243-250
  • DOI: 10.1007/s12185-015-1915-9
  • Peer Reviewed
• [Journal Article] Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first complete remission. (2016)
  • Author(s): Mizutani M, Hara M, Fujita H, Aoki J, Kanamori H, Ohashi K, Usuki K, Fukuda T, Chou T, Tanaka J, Atsuta Y, Takami A.
  • Journal Title: BMT (in press) Volume: NA Issue: 5 Pages: 645-53
  • DOI: 10.1038/bmt.2015.349
  • Peer Reviewed
• [Journal Article] Cytomegalovirus reactivation in low-grade B-cell lymphoma patients treated with bendamustine. (2016)
  • Author(s): Isono N, Imai Y, Watanabe A, Moriya K, Tamura H, Inokuchi K, Asano C, Masuda M, Shimura H, Mitsuhashi K, Kazama H, Sugimori H, Motoji T, Tanaka J
  • Journal Title: Leukemia and Lymphoma Volume: NA
  • Peer Reviewed
• [Journal Article] Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT. (2014)
  • Author(s): Kobayashi R, Tanaka J, Hashino S, Ota S, Torimoto Y, Kakinoki Y, Yamamoto S, Kurosawa M, Hatakeyama N, Haseyama Y, Sakai H, Sato K, Fukuhara T.
  • Journal Title: Bone Marrow Transplant. Volume: 49 Issue: 2 Pages: 254-257
  • DOI: 10.1038/bmt.2013.145
  • Peer Reviewed
• [Journal Article] Pre-transplant administration of imatinib for allogeneic hematopoietic stem cell transplantation in patients with BCR-ABL-positive acute lymphoblastic leukemia. (2014)
  • Author(s): Mizuta S, Matsuo K, Imai K, Nishiwaki S, kanamori H, Ohashi K, Fukuda T, Onishi Y, Miyamura K, Takahashi S, Onizuka M, Suzuki R, Atsuta Y, Morishima Y, Kato K, Sakamaki H, Tanaka J.
  • Journal Title: Blood Volume: 123 Issue: 15 Pages: 2325-2332
  • DOI: 10.1182/blood-2013-11-538728
  • Peer Reviewed
• [Journal Article] Risk factor analysis of non-Hodgkin lymphoma-associated haemophagocytic syndromes: a multicentre study. (2014)
  • Author(s): Sano H, Kobayashi R, Tanaka J, Hashino S, Ota S, Torimoto Y, Kakinoki Y, Yamamoto S, Kurosawa M, Hatakeyama N, Haseyama Y, Sakai H, Sato K, Fukuhara T.
  • Journal Title: Br J Haematol. Volume: 165 Issue: 6 Pages: 786-792
  • DOI: 10.1111/bjh.12823
  • Peer Reviewed
• [Journal Article] Analysis of outcomes following autologous transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia during the first complete remission. (2014)
  • Author(s): Kato H, Kawase T, Kako S, Mizuta S, Kurokawa M, Mori M, Ohashi K, Iwato K, Miyamura K, Hidaka M, Sakamaki H, Suzuki R, Morishima Y, Tanaka J.
  • Journal Title: Haematologica Volume: 99 Issue: 11 Pages: e228-e230
  • DOI: 10.3324/haematol.2014.108712
  • Peer Reviewed
• [Journal Article] Hepatitis B virus (HBV) reverse seroconversion (RS) can be prevented even in non-responders to hepatitis B vaccine after allogeneic stem cell transplantation: long-term analysis of intervention in RS with vaccine for patients with previous HBV infection (2014)
  • Author(s): Takahata M, Hashino S, Onozawa M, Shigematsu A, Sugita J, Fujimoto K, Endo T, Kondo T, Tanaka J, Imamura M, Teshima T
  • Journal Title: Transpl Infect Dis Volume: 16(5) Issue: 5 Pages: 797-801
  • DOI: 10.1111/tid.12283
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of kir ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without atg for acute leukemia in complete remission (2013)
  • Author(s): Tanaka J, Morishima Y, Takahashi Y, Yabe T, Oba K, Takahashi S, Taniguchi S, Ogawa H, Onishi Y, Miyamura K, Kanamori H, Aotsuka N, Kato K, Kato S, Atsuta Y, Kanda Y
  • Journal Title: Blood Cancer J Volume: 3 Issue: 11 Pages: 1-10
  • DOI: 10.1038/bcj.2013.62
  • Peer Reviewed
• [Journal Article] Reduced-intensity versus myeloablative conditioning allogeneic hematopoietic stem cell transplantation for patients aged over 45 years with acute lymphoblastic leukemia (ALL) in remission: A study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT). (2013)
  • Author(s): Tanaka J, Kanamori H, Nishiwaki S, Ohashi K, Taniguchi S, Eto T, Nakamae H, Minagawa K, Miyamura K, Sakamaki H, Morishima Y, Kato K, Suzuki R, Nishimoto N, Oba K, Masauzi N
  • Journal Title: Bone Marrow Transplant. Volume: 48 Issue: 11 Pages: 1389-1394
  • DOI: 10.1038/bmt.2013.68
  • Peer Reviewed
• [Presentation] ractionated ICE with Rituximab Is Safe and Effective for Relapse/Refractory DLBCL Patients with Severe Comorbidities. (2015)
  • Author(s): Tanaka N, Imai Y, Watanabe Y, Mitsuhashi K, Yoshinaga K, Shiseki M, Mori N, Tanaka J.
  • Organizer: 57th Annual Meeting of American Society of Hematology (ASH)
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Reduced PLCG1 expression Is Associated with Inferior Survival in Myelodysplastic Syndromes. (2015)
  • Author(s): Shiseki M, Ishii1 M, Ohwashi M, Yoshinaga K, Mori N, Tanaka J.
  • Organizer: 57th Annual Meeting of American Society of Hematology (ASH)
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Progression to myeloproliferative neoplasmas was associated with mutation of the JAK2 and CALR genes in patients with idiopathic leukocytosis and thrombocytosis. (2015)
  • Author(s): Mori N, Yoshinaga K, Ohwashi M, Shiseki M, Tanaka J.
  • Organizer: 20th Congressof Europian Hematology Association (EHA)
  • Place of Presentation: Vienna, Austria.
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia who had central nervous system involvement: A study from the adult ALL working group of the JSHCT. (2015)
  • Author(s): Shigematsu A, Kako S, Mitsuhashi K, Ohashi K, Uchida N, Fukuda T, Ogawa H, Miyamura K, Sakura T, Nagamura-Inoue T , Morishima Y, Ichinohe T, Atsuta Y, Mizuta S, Tanaka J.
  • Organizer: 20th Congressof Europian Hematology Association (EHA)
  • Place of Presentation: Vienna, Austria.
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] 造血細胞移植の移植免疫学―NK細胞の役割― ２０１４、１０、３１－１１、２：大阪 (2014)
  • Author(s): 田中淳司
  • Organizer: 第７６回 日本血液学会総会 教育講演
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] 抗腫瘍免疫とNK細胞 (2014)
  • Author(s): 田中淳司
  • Organizer: 第７６回 日本血液学会総会 ランチョンセミナー
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] KIR-ligand incompatibility in the graft-versus-host direction did not affect outcomes of single umbilical cord blood transplantation without ATG for acute leukemia in complete remission. (2013)
  • Author(s): Tanaka J, Takahashi Y, Yabe T, Morishima Y, Oba K, Takahashi S, Taniguchi S, Ogawa H, Ohnishi Y, Miyamura K, Kato K, Kato S, Atsuta Y, Kanda Y.
  • Organizer: 8th Congressof Europian Hematology Association (EHA)
  • Place of Presentation: Stockholm