IL-2 + cyclophosphamide + sirolimus

This is a combination therapy consisting of interleukin-2 (IL-2), cyclophosphamide, and sirolimus. Each component has a distinct mechanism of action: - IL-2 is a cytokine that promotes the proliferation and activation of T cells, particularly regulatory T cells (Tregs), which play a key role in immune tolerance. - Cyclophosphamide is an alkylating agent used as an immunosuppressant and chemotherapeutic; it depletes proliferating lymphocytes, including autoreactive T cells. - Sirolimus (also known as rapamycin) is an mTOR inhibitor that blocks IL-2-mediated signaling required for T-cell proliferation but does not inhibit IL-2-induced apoptosis. The combination aims to modulate the immune response by depleting pathogenic effector T cells while promoting or preserving regulatory T cell populations. This regimen has been studied in preclinical models for autoimmune diseases such as type 1 diabetes and IPEX-like syndromes, showing synergistic effects in preventing disease progression by shifting the balance from pro-inflammatory Th1 responses toward regulatory Th2/Th3 responses[1][2].