Forkhead box p3 (FoxP3) is a protein involved in regulation of immune system responses. FoxP3 functions as a master regulator for the development and function of regulatory T cells (Tregs), a subpopulation of T cells that modulate immune responses by suppressing induction and proliferation of effector T cells. Depletion or inactivation of FoxP3 results in inhibition of Tregs and improved effector T-cell activity in vitro and in vivo.
Tregs contribute to cancer by suppressing T effector cells, thereby compromising tumor killing and promoting tumor growth. Further, Tregs reduce the number of tumor-infiltrating lymphocytes within the tumor microenvironment, diminishing the efficacy of cancer immunotherapies. In cancer, circulating Tregs are often upregulated compared to healthy individuals. Disruption of FoxP3 regulation of Treg development and function in cancer patients reduces the circulating Treg population, thereby increasing T effector cell activity and improving the anti-tumor activity of immunotherapy.
FoxP3 homodimerization and interaction with co-activators is required for its transcriptional activity. Disruption of these protein-protein interactions inhibits transcription of genes required for Treg development and function, and results in enhanced anti-tumor immune responses. Sapience is targeting the interaction of FoxP3 homodimers with a peptide antagonist. Our FoxP3 antagonist peptides have demonstrated potent inhibition of FoxP3 gene transcription by reporter assay.