Transcription of 成人T細胞白血病リンパ腫に対する抗体療法 （抗 …
1 1 T CCR4 CCR4 (ATL) - 2010 2006 2010 CCR4 2 ATL T (ATL) ATL . ATL ( Tobinai et al, Abeloff s Clinical Oncology (ed 4) 2008:2425 ATL (2ndline )( ) (1stline )ATL MST 160% (0/4)CPT 1138% (5/13)2 Deoxycoformycin 32% (10/31*)Cladribine7% (1/15)* ATL Tsukasaki et al, J Clin Oncol 2007;25:5458 Ichihashi et al, Oncology 1992;49:333 Tsuda et al, Br J Cancer 1994;70:771 Tobinai et al, Jpn J Clin 1992;22:164 Tobinai et al, Int J Hematol 2003;77:5123 CCR4 CCR4 (KW 0761) KM2160 Imai et al, Int Immunol, 1999KM2760 Niwa et al, Cancer Res, 2004KW 0761 Ishii et al, Clin Cancer Res, 2010 Yamamoto et al, J Clin Oncol, 2010 Asn297 Asn297 Fucose ADCC Shinkawa et al, JBC 2003 CCR4 KW 0761 KW 0761 Extracellular regionsN terminalCCR4(CCchemokinereceptor4)Fucose AsnAsn297297 Fc ADCC POTELLIGENT CCR4 (CC chemokine receptor 4)ATL 90% ATL 4 2006 2008)KW 0761 ATL/PTCL 1 D1 8 15 22 ATL / PTCL(CCR4+)N=16 CohortDose(mg/kg)No.
2 Of pts(ATL)10013(2)No. of ptsORR(%)ALL CR (2) (4) (3) (2)Expanded (2)ATL/PTCL162331 ATL13 2231 2 : mg/kgYamamoto et al, J Clin Oncol 2010;28:1519 Hematological CR !! 10,000(/ L)KW 0761 ( mg/kg ) 103 68 5,000 (/ )01 22229365043158 ATL days5KW 0761 ( mg/kg ) 102 60 1 4 3 SD CR 401: 64 T (PTCL NOS)Hematological CR 3,0004,0005,000l counts 3) KW 0761 ( mg/kg ) 01,0002,0003,00018 15 22 29 36 43 50 DaysPeripheral cel( / mm3 (PTCL PTCL Day50 Day 5 Day1 Day50LN: < 25% : 6101102MM4660MF tumor stageATLacute44 PDSDSD PDSD CR291002+ # ofinfusionPB Skin LNORPFS(days)Response CCR4 1 1(0 01)102103201202203204301302303 MFMFMFMMF606855666657606469 ATL acuteATL acuteATL acuteATL acuteATL acuteATL acuteATL acuteATL acuteATL lymphoma444414444 CRCRPR CR SD PR CRPD CRSDSDSD PDSDSD CRPRSDSDPDCRPDPDPD100285503681071+362929 ( )2( )3( )401402403411412413 FFFMMF646264556258 PTCL NOSATL acuteATL lymphomaATL acuteATL acutePTCL NOS444444 CRCR CR CRCR PD PRPRSD SDPRPRSDPDCRSD812+644328714590+4( )Ex panted( ) ; (5/16; 2 CRs & 3 PRs) ; (7/16 )(Aug.))
3 , 2010 ) 7 2009 2010) ATLKW 076110/k /d(i ) CCR4 CCR4 2 (design #1) ATL mg/kg/day (iv) weekly x 8 FCM / IHCFCM / IHC CCR4 KW 0761, mg/kg D1 8 15 22 29 36 43 50 1 mos2 mos1 mos * (n=27) CTCAE 1 434 1 434 **10 2491126 50178018 GTP 304 10 4 Ca 203 50178018 ALT 20113214 AST 20105014 305108 Ca 013 **10 1 10 1 10 1 / (LDH )0314* ** Stevens Johnson ** 8 13CR**0PR0SD0PD0NE(%) (100 %) 13n * (n=26**) PR[95% CI]13 8335202041125010 / ()(63 %) 268125[25 92)(25 %)3[6 57](50 %)13[30 70]* Tsukasaki et al.]
4 (J Clin Oncol 2009;27:453)** 1 ** CRu (95% 5% : (ORR) 50% (95%CI 30 70) (P206); 55 , KW 0761 (cells/ L) CD4CD25400060008000 020000 1428425670 Time (days) (ATT ) ATL SSC HCCR49 (P206); 55 Day 6 Day 57 : mg/kgKW 0761 ( )(P206); 55 Day 57, Grade 1 Day 190, Grade 1 Day 141, Grade 2 (day57): , , HECD8 HE10 (P213); 69 mg/kgKW 0761 Day 5 Day 63 : (CRu)CCR4 2 . 2, 2010 ATL 27 26 KW 0761: 1. 0 mg/kg)27 50% (13/26.)
5 95% CI, 30 70%) : 8 5 (PFS) : 5 / (ALT, AST ) 11 mLSG15(VCAP/AMP/VECP)x4cyclesCCR4+ ID:NCT01173887 ATL 1stline ATL( 20yo) x 4 cyclesmLSG15 x 4 cycles+KW 0761(Bi weekly x 8)CCR4 CCR4 : (CR )CCR4+(n=44)Cli i lT i lIDNCT01192984T/NK T/NK ( 20 yo)KW mg/kg/day (iv) weekly x 8 CCR4 CCR4 CCR4+(n=35) ID:NCT01192984T/NK (CTCL ) : (ORR) (KW 0761)(2009 2010) / KW 0761 (2009 2010) CCR4 (KW 0761)(2006 2008)CCR4 Cancer Immunol Immunother, 2009 2010 ADCC CCR4 CCR4 in vitro ATL ADCCClin Cancer Res, 2005 Clin Cancer Res, 2004bCCR4 Treg CCR4 Cancer Res, 2006 Int J Cancer, 2007 Cancer Sci, 2006 J Clin Oncol, 2009J Immunol, 2009 CCR4; ATL Clin Cancer Res, 2003 CCR4.
6 T Clin Cancer Res, 2004aADCC CCR4 Cancer Res, 2004 Br J Haematol 2008 Clin Cancer Res 2007 Leukemia2006 ATL LNCCR4 staining2000 CCR4 199912 1 2 2 17 FCM CCR4 T *(2011 )* * CCR4 T (mLSG15) T/NK CTCL ) Phase II 13 CCR4 KW-0761 200132 3926153 6989145 7666418 1270595 CDR 4052515 7504104 7842797 1449850
