Modulating regulatory T cells By targeting Foxp3 enhancers (SJ-22-0010)

St. Jude Reference #SJ-22-0010

Description

Researchers at St Jude have discovered a new way to effectively modulate regulatory T (Treg) cell activity for therapeutic purposes. Treg cells are selected by targeting the genetic elements or enhancers of the Treg lineage specifying factor Foxp3 gene without affecting other cell types where Foxp3 gene is not expressed. To efficiently manipulate Treg’s function, pairs of Foxp3 enhancers are targeted simultaneously to enhance Treg lineage stability or to promote Treg induction efficiency. This can be achieved either by directly engineering the enhancer elements or by modulating the protein factors required for their molecular function. More innovative methods are now being developed (unpublished).

Treg cell function can be modulated in this way to treat many diseases including but not limited to autoimmune diseases, metabolic dysregulation, tissue regeneration, age-related neurodegeneration, and cancer. Manipulation of Treg cell function for therapeutic purposes has been a major goal for gene and cell therapies. Most methods use growth factors and cytokines to expand Treg cells or improve their function. However, because Treg cells are flexible in their lineage identity, these methods have very limited potential in treating autoimmune diseases because once Treg become effector T cells they exacerbate disease pathology. In addition, Treg cells are extremely diverse in their antigen specificity. It remains a challenge to treat the autoimmune diseases caused by impaired Treg cell repertoire diversity.

This invention stems from their research of the genetic elements controlling the expression of Treg lineage determining factor Foxp3. These elements generate a huge space for targeting and manipulating Treg cell function, including lineage stability and repertoire diversity. A biotechnology rapidly advances, with genome editing and cell-based therapies, the findings of the regulatory rules of Foxp3 genetic elements open new ways to more effectively engineer Treg cells, regarding their lineage stability and repertoire diversity, to improve the efficacy of Treg-based treatment. 

Keywords

Treg modulation, regulatory T cells, factor Foxp3 gene, chromatin looping, enhances or dampens Treg cell function, natural potency, autoimmune diseases, metabolic dysregulation, tissue regeneration, age-related neurodegeneration, cancer, gene therapy, cell therapy

Granted patents or published applications

US patent Application 2023/0183748 published Jun 15, 2023.

Related scientific references

X. Zong, X. Hao, et al. Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity. J Exp Med (2021) 218 (8): e20202415. https://doi.org/10.1084/JEM.20202415 - Published Online: 2021-06-04; Print: 2021-08-02.

Licensing opportunities

We are seeking partners to develop and use this invention for gene and cell therapies. Contact: chad.riggs@stjude.org

Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.