CAR-T実施
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1 Building a Clinical CAR-T Program - Jichi Medical University Experience
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4 Anti-CD3/28 mabs & IL-2: 29% Anti-CD3/28 beads: 66% Retroviral: 41% Lentiviral: 54% T-Flasks: 22% Static Culture Bags: 35% Rocking Motion Bioreactor: 43% Vormittag P, et al. Curr Opin Biotechnol
5 Chimeric Antigen Receptor : CAR l l l l l l l l l
6 Axicabtagene ciloleucel (KTE-C19) Tisagenlecleucel (CTL019)
7 NCI Axicabtagene ciloleucel FHCRC JCAR017 lisocabtagene maraleucel MSKCC JCAR015 ELIANA Tisagenlecleucel JULIET Tisagenlecleucel ZUMA-1 Axicabtagene ciloleucel TRANSCEND NHL001 JCAR017 lisocabtagene maraleucel ALL n= 20 ALL n=29 ALL n=53 ALL n=75 DLBCL n=93 DLBCL, TFL, PMBCL n=108 DLBCL, FL, MCL, PMSBCL n = 102 CR 70% MRD- 40% CR 100% MRD- 93% CR 83% MRD- 67% CR 81% MRD- 95% Best ORR 52% Best CR 40% Best ORR 82% Best CR 58% Best ORR 80% Best CR 50% Lee DW, el al.: Lancet, 2015 Turtle CJ, el al: J Clin Invest, 2016 Park JH, el al: N Engl J Med, 2018 Maude SL, el al: N Engl J Med, 2018 Schuster SJ, el al : N Engl J Med, 2019 Neelapu SS, el al : N Engl J Med, 2017 Abramson, et al : ASCO 2018 NCT NCT NCT NCT NCT NCT NCT
8 4-1BBζ CAR l l Circulating T cells CD28ζ CAR l l Time Omkar Kawalekar, Immunity 2016 B-ALL, n = 47 CD28, n=19 4-1BB, n=28 ORR 89% 100% CAR-T peak (FCM) CRS (G3, 4) 5 0 NT (G3, 4) 5 0 Lu Pet al. ASCO 2018 Abstr 3041
9 Henriksson MM et al. Transfusion and Apheresis Science 2016
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12 ELIANA Tisagenlecleucel MSKCC JCAR015 CR+CRi : 81% (61/ 75) ITT : CR+CRi : 66% ( 61/ 92) Time from enroll to infusion: 45d (30-105) CR: 83% (44/ 53) ITT : CR : 54% ( 45/ 83) Time from enroll to infusion: 74d (44-312) Maude SL et al. NEJM 2018 Park JH et al. NEJM 2018
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14 SOP/ workflow / slide / pamphlet
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16 0 ADC) a 0 2y 1R 1d3(y 074T07y
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18 NCI Axicabtagene ciloleucel FHCRC JCAR017 lisocabtagene maraleucel MSKCC JCAR015 ELIANA Tisagenlecleucel JULIET Tisagenlecleucel ZUMA-1 Axicabtagene ciloleucel TRANSCEND NHL001 JCAR017 lisocabtagene maraleucel ALL n= 20 ALL n=30 ALL n=53 ALL n=75 DLBCL n=93 DLBCL, TFL, PMBCL n=108 DLBCL, FL, MCL, PMSBCL n = % total 28% severe 83% total 23% severe 85% total 26% severe (1 Pt G 5) 77% total 57% total 18% severe 93% total 18% severe 37% total 18% severe 29% total 50% severe 42% G % total 13% G3 39% total 11% grade % total 28% G3 23% total 13% G3 Lee DW, el al.: Lancet, 2015 Turtle CJ, el al: J Clin Invest, 2016 Park JH, el al: N Engl J Med, 2018 Maude SL, el al: N Engl J Med, 2018 Schuster SJ, el al : N Engl J Med, 2019 Neelapu SS, el al : N Engl J Med, 2017 Abramson, et al : ASCO 2018
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20 Lee DW et al. Bio; Blood Marrow Transplant. : 1S (18): , 2018 IL-6, IL-1, IL-8 IL-10, TNF-α Activation IFN-γ/TNF-α T cell Macrophage Dendritic cell Tumor cell CAR- T Macrophage T cell CAR Endothelial cell Macrophage IFN-γ TNF-α Shimabukuro-Vornhagen A: Journal of Immunotherapy of Cancer : 6(1): 56, 2018
21 Lee DW et al. Bio; Blood Marrow Transplant. : 1S (18): , 2018
22 Lee DW et al. Bio; Blood Marrow Transplant. : 1S (18): , 2018
23 Neelapu SS: Nat Rev Clin Oncol: 15(1): 47-62, 2018
24 Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)
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26 Torre M et al. : J Neuropathol Exp Neurol: 77(10): , 2018
27 Lee DW et al. Bio; Blood Marrow Transplant. : 1S (18): , 2018
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30 Angiopoietin-1 IL-8 35 Angiopoietin-2 CX3CL1 Fractalkine gp130 IL-10 IL-12 IL GM-CSF IP-10 CXCL-10 CRG-2 20 IFNγ IL-1α IL-18 MCP-1 CCL2 15 IL-1β MIP-1α CCL3 10 IL-2 IL-2Rα/CD25 IL-5 IL-6 PDGF-BB RAGE TNFα TNFR2 5 0 pre
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INDEX April. 2013 No.113 Contents 2.20 WED 2.16 SAT T opics! Aizawa Event Calendar 5 May TUE 5.14 TUE 5.28 TUE 6.11 6 13 20 27 5 12 19 26 7 14 21 28 1 8 15 22 29 2 9 16 23 30 3 10 17 24 31 4 11 18 25 MON
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DR. KAZUMOTO IGUCHI & FAMILY'S WHAT'S NEW
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上原記念生命科学財団研究報告集, 23(2009) 190. CD4 + ヘルパー T 細胞の選択的活性化 西川博嘉 Key words:cd4 + ヘルパー T 細胞,CD4 + 制御性 T 細胞, 癌 精巣抗原,co-stimulatory molecules, 抗体療法 三重大学大学院医学系研究科寄付講座がんワクチン講座 緒言 1991 年ヒト腫瘍抗原遺伝子の存在が報告されて以来, これらの腫瘍特異抗原を用いた悪性腫瘍に対する免疫療法が注目を集めている.
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DR. KAZUMOTO IGUCHI & FAMILY'S WHAT'S NEW
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Contents 01 02 03 04 06 11 14 20 26 30 31 32 Outline Message Opening Event Exhibit Categories/ Floor Map 1F Hall 8 Hall 7 Hall 6 Hall 5 Hall 4 Hall 3 Hall 2 Hall 1 201 2F 2F 1F 301 302 303 304 CEATEC
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