IMMUNOLOGY2026™ Conference Recordings For Attendees-Identification of a FoxP3-specific small molecule degrader with potent antitumor immunotherapeutic efficacy

Identification of a FoxP3-specific small molecule degrader with potent antitumor immunotherapeutic efficacy

Video Transcription

Video Summary

The speaker presented a new small molecule, FDO3, designed to selectively degrade FOXP3, the key transcription factor in regulatory T cells (Tregs) that suppress anti-tumor immunity. The lab screened 640 compounds and found that FDO3 reduced FOXP3 levels by promoting Stub1-mediated ubiquitination and proteasomal degradation. In induced Tregs, FDO3 lowered FOXP3, shortened its half-life, increased ubiquitination, and weakened Treg suppressive function, allowing better CD8 T-cell proliferation. In human Tregs, similar FOXP3 reduction and marker changes were observed. In naturally derived Tregs, degradation required an inflammatory signal, interferon gamma, suggesting context-dependent activity. In mouse tumor models, local or systemic FDO3 treatment reduced tumor growth, increased effector T-cell function, and selectively decreased FOXP3 in tumor-infiltrating Tregs without major effects on peripheral Tregs. The study proposes FDO3 as a promising immunotherapeutic strategy for targeting tumoral Tregs.

Meta Tag

Date April 18, 2026 1:00 PM - 1:15 PM

Room 205

Session Molecular Mechanisms of Tumor Immunity

Speaker Amy Tang

Track Tumor Immunology: Checkpoints, Prevention, And Treatment (TIPT)

Year 2026

Keywords

FDO3

FOXP3 degradation

regulatory T cells

tumor immunotherapy

ubiquitination

April 18, 2026 1:00 PM - 1:15 PM

205

Molecular Mechanisms of Tumor Immunity

Amy Tang

Tumor Immunology: Checkpoints, Prevention, And Treatment (TIPT)

2026