*Purpose: Vascularized composite allotransplantation (VCA) is challenged by the morbidity of non-specific immunosuppression required to prevent rejection. The use of highly specific biologics has not been well explored in VCA. Given that psoriasis is T-cell mediated, as is rejection of skin-containing VCAs, we sought to assess the role of two biologics, ustekinumab and secukinumab, which are approved to treat psoriasis by inhibiting Th17 cells.

*Methods: We combined these agents with belatacept and steroids in a VCA non-human primate model. The study included 3 groups. Group I consisted of Belatacept and Steroids, group II was Belatacept, Ustekinumab with steroid taper, and group III was Belatacept, Secukinumab with steroid taper.

*Results: Three animals were transplanted in each group. In group I, the mean graft survival time until the first sign of rejection was 10 days whereas in group II and III it was 10.33 and 11 days respectively. The immunohistochemistry analysis result showed that the number of IL-17a⁺ cells and the intensity of IL-17a expression were significantly reduced in both dermis and hypodermis parts in groups II and III when compared to group I (P<0.01).

*Conclusions: Ustekinumab and secukinumab led to less T-cell infiltration and IL-17a expression in the allograft but provided no benefit to belatacept and steroids in VCA survival. These pilot data inform the role of Th17 cell inhibition in addition to costimulation molecule-focused therapies to directly targeting the unique components of T-cell mediated rejection of VCA.

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