Alloreactive NK-cells activity to leukemia with HLA-LOH after HLA haplomismatch stem cell transplantation
| Project/Area Number |
23591536
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Seiji 名古屋大学, 大学院医学系研究科, 教授 (20313992)
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| Co-Investigator(Renkei-kenkyūsha) |
OGAWA Seishi 京都大学, 大学院医学研究科, 教授 (60292900)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 白血病 / NK細胞 / GVL効果 / KIR / 造血幹細胞移植 / HLA |
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| Research Abstract |
We investigated HLA expression on leukemic blasts derived from patients at diagnosis and relapse after hematopoietic stem cell transplantation (HSCT) using flow cytometry with locus-specific antibodies. HLA expression analysis was useful for analysis of donor chimerism and minimal residual diseases. We found that leukemic blasts with HLA-LOH at relapse were efficiently killed by donor NK cells. This was partially explained because ULBP2 on the leukemic blasts with HLA-LOH was highly expressed. We could monitor single KIR positive NK cells that are not inhibited by patient's HLA. Increased single KIR positive NK cells were related to higher NK cell alloreactivity. Finally, GMP grade NK cell expansion method was established using FDA approved gene modified K562 cells. These findings could establish the rationale of allogeneic NK cell therapy using KIR mismatched donor NK cells.
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Report
(4 results)
Research Products
(68 results)
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[Journal Article] Rabbit antithymocyte globulin and cyclosporine as first-line therapy for children with acquired aplastic anemia2012
Author(s)
Takahashi Y, Muramatsu H, Sakata N, Hyakuna N, Hamamoto K, Kobayashi R, Ito E, Yagasaki H, Ohara A, Kikuchi A, Morimoto A, Yabe H, Kudo K, Watanabe K, Ohga S, Kojima S
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Journal Title
Blood
Volume: 121(5)
Issue: 5
Pages: 862-3
DOI
Related Report
Peer Reviewed
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[Journal Article] Zoledronate sensitizes neuroblastoma-derived tumor-initiating cells to cytolysis mediated by human gammadelta T cells2012
Author(s)
Nishio N, Fujita M, Tanaka Y, Maki H, Zhang R, Hirosawa T, Demachi-Okamura A, Uemura Y, Taguchi O, Takahashi Y, Kojima S and Kuzushima K.
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Journal Title
J Immunother
Volume: 35(8)
Issue: 8
Pages: 598-606
DOI
Related Report
Peer Reviewed
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[Journal Article] Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia2012
Author(s)
Doisaki S, Muramatsu H, Shimada A, Takahashi Y, Mori-Ezaki M, Sato M, Kawaguchi H, Kinoshita A, Sotomatsu M, Hayashi Y, Furukawa-Hibi Y, Yamada K, Hoshino H, Kiyoi H, Yoshida N, Sakaguchi H, Narita A, Wang X, Ismael O, Xu Y, Nishio N, Tanaka M, Hama A, Koike K, Kojima S
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Journal Title
Blood
Volume: 120
Issue: 7
Pages: 1485-1488
DOI
Related Report
Peer Reviewed
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[Journal Article] Excellent outcome of allogeneic bone marrow transplantation for Fanconi anemia using fludarabine-based reduced-intensity conditioning regimen2012
Author(s)
Shimada A, Takahashi Y, Muramatsu H, Hama A, Ismael O, Narita A, Sakaguchi H, Doisaki S, Nishio N, Tanaka M, Yoshida N, Matsumoto K, Kato K, Watanabe N and Kojima S.
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Journal Title
Int J Hematol
Volume: 95(6)
Issue: 6
Pages: 675-679
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA-identical related donors2011
Author(s)
Watanabe N, Takahashi Y, Matsumoto K, Horikoshi Y, Hama A, Muramatsu H, Yoshida N, Yagasaki H, Kudo K, Horibe K, Kato K and Kojima S.
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Journal Title
Pediatr Transplant
Volume: 15(6)
Issue: 6
Pages: 642-649
DOI
Related Report
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