CD73 / IL-2Rβγ

Class

anti-CD73 antibody-IL-2 variant bispecific fusion protein

Pathway

blockade of adenosine-mediated immunosuppression + IL-2-driven T-cell activation

This mechanism combines two immune-modulating strategies in a single bispecific fusion protein. CD73 is an enzyme on the surface of tumor and immune cells that converts extracellular AMP into adenosine, a signaling molecule that binds receptors on T cells and dampens their activity. Tumors frequently exploit this pathway to create a locally immunosuppressive environment that helps them evade immune attack. Blocking CD73 removes this brake. The second component targets IL-2Rβγ, a receptor complex found on effector T cells and natural killer cells that, when engaged by interleukin-2 (IL-2), drives their proliferation and cytotoxic activity. By using an engineered IL-2 variant biased toward this receptor complex rather than the full high-affinity IL-2 receptor found on regulatory T cells, the fusion protein aims to stimulate immune effector cells preferentially while limiting activation of cells that suppress immune responses. Combining CD73 blockade with targeted IL-2Rβγ stimulation is intended to simultaneously relieve adenosine-mediated suppression and actively promote cytotoxic immune activity, an approach relevant across solid tumors where adenosine accumulation and insufficient effector cell activity both limit anti-tumor immunity.