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This CNI-free immunosuppressive regimen was developed by Ospedale San Raffaele specifically for patients with type 1 diabetes mellitus undergoing pancreatic islet transplantation. The protocol aims to replace standard calcineurin inhibitors (CNIs), which can be nephrotoxic and detrimental to islet cell function, with a combination of sirolimus (an mTOR inhibitor), mycophenolate mofetil (an antimetabolite), anti-thymocyte globulin (ATG, for T-cell depletion), and anakinra (an IL-1 receptor antagonist). This specific combination is designed to create a permissive environment for islet graft survival and the potential expansion of regulatory T cells (Tr1 cells) to promote immune tolerance. The regimen includes an induction phase with ATG and anakinra, followed by maintenance therapy with sirolimus and mycophenolate mofetil.
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