CTLA-4 (antibody moiety) + IL-2Rβ (via IL-15/IL-15Rα fusion)

Class

CTLA-4-targeted antibody-IL-15 fusion protein (immunocytokine)

Pathway

ADCC-mediated depletion of CTLA-4-expressing (e.g. Treg) cells combined with IL-15 trans-presentation to expand/activate CD8+ T and NK cells

This molecule is a bifunctional immunocytokine that pairs two anti-tumor immune strategies in one protein: an antibody arm directed against CTLA-4, a checkpoint receptor most highly expressed on regulatory T cells (Tregs), and a cytokine arm built from interleukin-15 (IL-15) fused to its receptor alpha subunit, which engages the IL-2 receptor beta chain found on cytotoxic CD8+ T cells and natural killer (NK) cells. The antibody portion can flag CTLA-4-bearing cells for destruction through antibody-dependent cellular cytotoxicity (ADCC), a process in which immune effector cells recognize the antibody's tail and kill the targeted cell. Because Tregs suppress anti-tumor immunity, depleting them removes a brake on the immune response. Simultaneously, the IL-15 component stimulates the proliferation and cytotoxic activity of CD8+ T cells and NK cells, the effector populations responsible for killing tumor cells. Combining depletion of suppressive cells with activation of effector cells in a single molecule is intended to produce a coordinated shift in the tumor immune balance, relevant across many solid tumor types where regulatory T cell infiltration and effector cell exhaustion limit the effectiveness of checkpoint blockade alone.