Interleukin-2 (IL-2) is a pleiotropic cytokine—cytokine that exerts different types of responses on different cell types—that can activate or suppress immune responses depending on the target cell types. Clinically, IL-2 is an FDA-approved drug for metastatic renal cell carcinoma and melanoma. Further expansion of its therapeutic potential was hindered by its serious side effects. Protein engineering of IL-2 has attracted significant attention in recent years to develop new IL-2 therapeutics with better safety profiles. Earlier this year, bempegaldesleukin, a pegylated IL-2 aiming to bind toward the dimeric IL-2 receptor from naive T cells and NK cells, failed in phase 3 trials. Nonetheless, several IL-2 bioconjugates, immunocytokines, and fusion proteins are currently in cancer-focused clinical trials. Built upon these efforts, Drs. Chou and Everett propose to develop a new-generation IL-2 therapeutic: stimuli-responsive IL-2, where the cellular activity of IL-2 can only be activated by a specific stimulus. Through the support of the SCI Women's Cancer Center Innovation award, they will build PD-1-responsive IL-2, where the in vivo activity of IL-2 will only be activated in an environment with abundant PD-1 presence. In all other tissues with little or no PD-1 expression, the PD-1-responsive IL-2 cannot bind to IL-2R. These new IL-2 molecules may provide on-target efficiency while minimizing side effects.
Funding Opportunities
SCI Innovation Awardee
March 2023 - SCI Women’s Cancer Center Innovation Award