Stanford Cancer Institute

SCI Innovation Awardee

March 2023 - SCI Women’s Cancer Center Innovation Award

A $50,000 Stanford Women's Cancer Center Innovation award was awarded to Danny Chou, PhD, Assistant Professor of Pediatrics and, by courtesy, of Chemical and Systems Biology, and his collaborator Everett Meyer, MD, PhD, Associate Professor of Medicine, for their project entitled “Inserting a switch into IL-2 to develop PD-1-dependent immunotherapy.” Dr. Chou is interested in using chemical and enzymatic synthesis to create novel chemical entities with enhanced properties with the ultimate goal of translating his discoveries into therapeutic interventions in human diseases.

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.