20P αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity via rejuvenating tumor infiltrating T cells

Cytokines possess remarkable therapeutic potential in cancer immunotherapy; however, their clinical application has been severely hampered by structural instability in vitro and in vivo, short half-life, and more importantly, severe systemic toxicity that occur before achieving durable tumor control. Recent studies have been exploring bispecific antibodies that mimic cytokine signaling by engaging and cross-linking cytokine receptors in vitro. Nevertheless, their pharmacokinetics (PK), pharmacodynamics (PD), and critically, their functional role in antitumor immunity remains unclear in the absence of rigorous in vivo evaluation.