CAR-T実施
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- あけなお おおはし
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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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DR. KAZUMOTO IGUCHI & FAMILY'S WHAT'S NEW
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フローサイトメーターによる多タンパク同時定量解析キット BioLegend is ISO 9001:2008 and ISO 13485:2003 Certified World-Class Quality Superior Customer Support Outstanding Value 02-0009-02j LEGENDplex の特長 LEGENDplex は 一つのサンプルから多の可溶性タンパクを同時に定量できるフローサイトメーター用ビーズアッセイキットです
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