αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.

αTIGIT-guided IL-15 mimetics significantly enhance antitumor immunity, achieving potent effects without systemic toxicity in vivo.

• Why it matters: Cytokines' therapeutic potential is limited by instability, toxicity, and poor drug-like properties, necessitating safer, more effective immune activators for cancer treatment.
• What they did: Using immunized alpaca-derived phage display, structural screening, and format comparisons, researchers engineered bispecific IL-15 mimetics, including a tri-antibody design targeting TIGIT and IL-15 receptors, tested in vitro and in vivo.
• The result: The αTIGIT-αIL-15Rβγ mimetic markedly improved CD8+ T cell activity and increased intratumoral stem-like T cells, enabling safer, more effective cytokine immunotherapy compatible with immune checkpoint blockade.