IL-2/anti-IL-2 antibody conjugate SLC-3010

A noncovalent conjugate consisting of the cytokine interleukin-2 (IL-2; IL2) and TCB2, a humanized antibody directed against the IL-2 receptor subunit alpha (IL2Ra; CD25) binding site on IL-2, with potential immunomodulatory and antineoplastic activities. Upon administration of IL-2/anti-IL-2 antibody conjugate SLC-3010, the IL-2 moiety binds to the IL-2 receptor beta (CD122) and gamma (CD132) subunit (IL2Rb/g) expressed on CD8+ T-effector cells and natural killer (NK) cells, thereby activating IL2Rb/g-mediated signaling within these immune cells. This activates cytotoxic T lymphocytes (CTLs) and NK cells and induces expression of certain cytotoxic cytokines, such as interferon-gamma (IFNg) and transforming growth factor-beta (TGFb). This leads to T-cell-mediated cytotoxic immune responses against tumor cells and inhibition of tumor cell proliferation. The TCB2 moiety binds to the IL2Ra binding site on IL-2, preventing the binding of IL-2 to IL2Ra expressed on regulatory T lymphocytes (Tregs). Signaling through IL2Ra activates CD4-positive immunosuppressive Tregs, which would suppress tumor cell killing. In addition, the binding of the TCB2 moiety to IL-2 induces an allosteric effect that increases the binding affinity of IL-2 to the heterodimeric IL2Rb/g, which further activates T-cell-mediated cytotoxic immune responses against tumor cells.