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Rituxan + siplizumab + ATGAM + cyclophosphamide + tegoprubart (the Sip-Tego regimen) is an investigational multi-drug conditioning protocol used to induce donor-specific immunologic tolerance in recipients of combined kidney and bone marrow transplants. Developed by researchers at Massachusetts General Hospital, the regimen combines several immunosuppressive and immunomodulatory agents: rituximab (a CD20-targeting monoclonal antibody for B-cell depletion), siplizumab (an anti-CD2 monoclonal antibody that modulates T and NK cells), ATGAM (equine anti-thymocyte globulin for T-cell depletion), cyclophosphamide (an alkylating agent for lymphodepletion), and tegoprubart (a CD40L/CD154-blocking antibody to prevent costimulation). The primary goal of this regimen is to facilitate mixed hematopoietic chimerism, allowing the patient's immune system to coexist with the donor organ without the need for lifelong maintenance immunosuppression. It is currently being evaluated in a Phase 1 clinical trial for adult patients with end-stage renal disease (ESRD).
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