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Siplizumab + methylprednisolone is an investigational combination therapy comprising siplizumab (also known as MEDI-507), a humanized IgG1 monoclonal antibody targeting the CD2 receptor, and methylprednisolone, a synthetic glucocorticoid corticosteroid[1][6][7]. Siplizumab binds CD2 on T cells and NK cells, blocking the CD2–LFA-3 interaction, inhibiting T-cell activation, and promoting depletion of effector memory T cells (via antibody-dependent cellular cytotoxicity). It also spares naïve and regulatory T cells, shifting the immune balance toward regulatory populations[6][7]. Methylprednisolone adds potent anti-inflammatory and immunosuppressive action by modulating gene transcription and suppressing multiple inflammatory cell types[1]. The combination has been studied in the context of allogeneic stem cell transplantation and hematologic malignancies to induce mixed chimerism and suppress graft-versus-host disease[1]. Siplizumab was originally developed by MedImmune and later by ITB-Med Biopharmaceuticals[7]; methylprednisolone is a widely available generic drug.
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