Table 2.

Costimulation blockade.

Large Animal Model	VCA model	IS	Experimental Groups	Results/Conclusions	Reference
Yucatan miniature swine	Hind limb VCA	Leukocyte Depletion: TBI and TI	Group 1 - no treatment; Group 2 - Tacrolimus only; Group 3 - irradiation, BMT, and FK506; Group 4 - received Tacrolimus and CTLA4-Ig	Group 1 survival: 5-8 days	(40)
		Cell infusion: Animal groups received 15, 30, or 60 million cells per kilogram of whole unmodified BM.		Group 2 survival: 30 – 32 days (only skin and muscle rejected)
		Immunosuppression: CTLA4Ig.		Group 3 survival 5-53 days (only skin rejected).
				Group 4 survival: > 150 days (skin survival in 2/3 animals > 150 days).
				Addition of CTLA4-Ig to calcineurin inhibitors significantly prolonged survival of VCA grafts.
Rhesus Macaque	Radial forearm VCA	Belatacept, Steroids, Ustekinumab (Anti-IL12/23, Secukinumab (anti-IL17A)	Group 1 - Belatacept and steroids; Group 2 - Belatacept, Ustekinumab with steroid taper; Group 3 - Belatacept, Secukinumab with steroid taper.	Group 1 survival: 10 days	(41)
				Group 2 survival: 10.33 days
				Group 3 survival: 11 days
				Ustekinumab and secukinumab were associated with decreased T-cell infiltration and IL-17a expression in the allograft but had no impact on VCA survival in the setting of Belatacept and steroids.
Rhesus Macaque	Radial forearm VCA	Belatacept/CTLA4Ig vs. Tacrolimus	Group 1 – Tacrolimus; Group 2 – CTLA‐4Ig, alefacept, sirolimus; Group 3 – CTLA‐4lg, alefacept, tacrolimus conversion to sirolimus; Group 4 – Belatacept, alefacept, tacrolimus conversion to sirolimus; Group 5 – Belatacept, tacrolimus conversion to sirolimus.	CoB was superior to calcineurin inhibitors in prolonging VCA survival.	(42)
				Sirolimus was associated with healing complications resulting in lack of VCA engraftment.

IS, immunosuppression; TBI, total body irradiation; TI, thymic irradiation; RBC, red blood cells; VCA, vascularized composite allotransplant; BM, bone marrow; CoB, co-stimulation blockade; Ig, immunoglobulin.