Inducing plasticity to prime immune system for CAR-Treg therapy


Project ID: D2022-28


Regulatory T cells (Tregs) are the critical regulators of peripheral immune tolerance; when defective, Tregs can lead to autoimmune disorders, such as Type 1 Diabetes (T1D) A more recent approach to prevent/treat autoimmunity is to refit immune cells towards their non-inflammatory phenotype in the affected organ. Chimeric Antigen Receptor (CAR) T cells were developed with antigens that make the cells organ-specific. For CAR-Treg treatments to be more effective, it is ideal for the patient’s body to grow/expand the CAR-Treg population added during treatment. Current methods to expand CAR-Tregs are nascent, but typically cause an increase in other toxic cells. Therefore, there is a need for a safer way to expand exogenously administered Tregs.

Invention Description

Researchers at the University of Toledo have developed a way to induce plasticity of effector T cells (Teffs) to prime the immune system for CAR-Treg therapy. elF5A and Notch signaling inhibition favors the reversal of the pro-inflammatory milieu, enriching the Treg cells in the microenvironment, and restraining the antigen-specific CD8-mediated destruction of healthy cells.

Synergistic therapy inhibiting eIF5A and Notch pathways leads to in vivo enrichment of Treg cells through T-cell receptor mediated activation. In our T1D studies, it was shown that these interventions tip the pro-inflammatory balance toward regulation and protect/rescue T1D mouse islet β-cells.


- Pretreatment therapy for CAR-Treg treatments

- Safely expanding in vivo CAR-Tregs


- Does not activate cytotoxic cells

- Can use with low levels of host cell antigen expression


Publication:                Immune Cell Plasticity Allows for Resetting of Phenotype From Effector to Regulator With Combined Inhibition of Notch/EIF5A Pathways. Front.                                     Cell Dev. Biol., 22 November 2021 Sec. Molecular and Cellular Oncology

Patent Information:
For Information, Contact:
Katherine Pollard
Licensing Associate
The University of Toledo
Shahnawaz Imam
Juan Jaume
Chimeric Antigen Receptor