The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation

Table 2

Selected studies using anti-CD154mAb in pig-to-nonhuman primate xenotransplantation.

First author (year)	Donor pig	Recipient NHP	Immunosuppressive regimen	Longest survival (days)
Heart xenotransplantation, heterotopic
Buhler (2000) [86]	WT	Baboon	TBI, TI, splenectomy, IA, ATG, CVF, CSA, or anti-CD154mAb, MMF +/− pig stem cells	N.A
Houser (2004) [87]	CD55	Baboon	ATG, anti-CD2mAb, TI, CVF, anti-CD154mAb, MMF, CS	139
Dor (2005) [88]	GTKO	Baboon	ATG, anti-CD154mAb, MMF, CS	179
Kuwaki (2005) [89]	GTKO	Baboon	ATG, anti-CD2mAb, TI, CVF, anti-CD154mAb	179
Wu (2005) [90]	CD46	Baboon	ATG, anti-CD154mAb, +/− anti-CD20mAb +/− CTLA4-Fc	11
Wu (2007) [91]	CD46	Baboon	ATG, anti-CD154mAb, GAS194 or TPC, +/− IA	36
Ezzelarab (2009) [92]	GTKO	Baboon	ATG, CVF, anti-CD154mAb, MMF, CS	56
Mohiuddin (2012) [93]	GTKO.CD46	Baboon	ATG, anti-CD20mAb, anti-CD154mAb, MMF, CS	236
Kim (2013) [94]	GTKO	Cynomolgus	ATG, anti-CD20mAb, anti-CD154mAb, tacrolimus, CS	24
Ezzelarab (2015) [95]	GTKO	Baboon	ATG, anti-CD154mAb, MMF	56
Iwase (2015) [96]	GTKO.CD46.TBM	Baboon	ATG, anti-CD20mAb, anti-CD154mAb, MMF, CS	52
Kidney xenotransplantation
Buhler (2000) [86]	WT	Baboon	TBI, TI, splenectomy, IA, ATG, CVF, CSA, or anti-CD154mAb, MMF +/− pig stem cells	N.A
Buhler (2001) [97]	CD55	Baboon	TBI, TI, splenectomy, IA, ATG, CVF, anti-CD154mAb, MMF, CS	29
Barth (2003) [98]	CD55	Baboon	Thymokidneys, anti-CD2mAb, ATG, anti-CD154mAb, CyP, CVF, MMF, CS	229
Gollackner (2003) [99]	CD55	Baboon	TI, splenectomy, IA, ATG, anti-CD154mAb, CyP, CVF, MMF, CS	13
Knosalla (2003) [100]	CD55	Baboon	TI, splenectomy, IA, ATG, anti-CD154mAb, CyP, CVF, MMF, CS	29
Yamada (2005) [75]	GTKO	Baboon	Vascularized thymic lobe, WBI, anti-CD2mAb, anti-CD154mAb, MMF, CS, CVF	68
Shimizu (2005) [101]	CD55	Baboon	Thymokidneys, splenectomy, IA, anti-CD3mAb, ATG, anti-CD154mAb, CyP, CVF, MMF	30
Griesemer (2009) [102]	GTKO	Baboon	Thymectomy, splenectomy, TBI, ATG, anti-CD2mAb, anti-CD154mAb, tacrolimus, MMF, anti-CD20mAb	83
Lin (2010) [103]	GTKO.CD46	Baboon	ATG, antiCD154mAb, MMF, CVF, CS	16
Nishimura (2011) [104]	GTKO	Baboon	Thymokidney, thymectomy, splenectomy, anti-CD3, antiCD2mAb, ATG, anti-CD20mAb, tacrolimus, MMF, anti-CD154mAb	15
Ezzelarab (2015) [95]	GTKO	Baboon	ATG, anti-CD154mAb, MMF	10
Higginbotham (2015) [22]	GTKO.CD55	Rhesus	Anti-CD4, anti-CD8, anti-CD154mAb, MMF, CS	310
Kim (2017) [76]	GTKO.CD55	Rhesus	Anti-CD4, anti-CD8, anti-CD154mAb, MMF, CS	405
Liver xenotransplantation
Kim (2002) [105]	GTKO	Baboon	ATG, LoCD2b, CVF, anti-CD154mAb, azathioprine, tacrolimus, CS	9
Navarro-Alvarez (2016) [106]	GTKO	Baboon	ATG, LoCD2b, CVF, anti-CD154mAb, tacrolimus, CS	6
Islet xenotransplantation
Buhler (2002) [18]	WT	Baboon	Splenectomy, IA, TBI, ATG, CVF, anti-CD154mAb, CSA, MMF, CS	28
Hering (2006) [107]	WT	Cynomolgus	Anti-CD25mAb, FTY720, rapamycin, anti-CD154mAb	187
Cardona (2006) [108]	WT	Rhesus	Anti-CD25mAb, anti-CD154mAb, CTLA4-Ig	>260
Rood (2007) [109]	GTKO	Cynomolgus	ATG, CVF, anti-CD154mAb, MMF, tacrolimus	>58
Casu (2008) [110]	WT	Cynomolgus	ATG, anti-CD154mAb, MMF	>60
van der Windt (2009) [19]	CD46	Cynomolgus	ATG, anti-CD154mAb, MMF	396
Thompson (2011) [20]	GTKO	Rhesus	Anti-CD154mAb, anti-LFA1mAb, MMF, belatacept	249
Bottino (2014) [111]	GTKO.CD46. TFPI.CTLA4Ig.CD39	Cynomolgus	ATG, MMF, anti-CD154mAb, CS	365
Shin (2015) [112]	WT	Rhesus	Anti-CD154mAb, ATG, rapamycin, CVF, adalimumab	>603

ATG: antithymocyte globulin; CS: corticosteroids; CSA: cyclosporine A; CVF: cobra venom factor; CyP: cyclophosphamide; NHP: nonhuman primate; TBI: total body irradiation; TI: thymus irradiation; mAb: monoclonal antibody; MMF: mycophenolate mofetil; mAb: monoclonal antibody; GTKO: α1,3-galactosyltransferase gene knockout; GAS914: a soluble glycoconjugate comprising Gal on poly-L-lysine backbone; N.A: not applicable; TBM: thrombomodulin; TPC: an aGal-polyethylene glycol polymer conjugate; WT: wild-type.