mTOR Inhibitor Everolimus in Regulatory T Cell Expansion for Clinical Application in Transplantation

Area of Science:

• Immunology
• Cell Therapy
• Transplantation Medicine

Background:

• Adoptive transfer of regulatory T (Treg) cells shows promise for inducing tolerance and improving graft survival in transplant recipients.
• A novel clinical trial is investigating ex vivo expanded autologous Treg cells for renal transplant recipients on an everolimus (EVR)-based immunosuppressive regimen.

Purpose of the Study:

• To determine the mechanisms of action and efficacy of EVR for developing Treg cell-based adoptive immunotherapy.
• To integrate EVR into both in vivo and ex vivo Treg cell expansion protocols for transplantation.

Main Methods:

• CD25 Treg cells were cultured with EVR or rapamycin (RAPA) for short (5-day) or long (21-day) periods.
• Multi-parametric flow cytometry, Western blot, and extracellular flux analysis were used to assess Treg cell expansion, phenotype, function, and signaling pathways.

Main Results:

• EVR-treated cells exhibited transiently slower growth and reduced metabolic activity compared to RAPA-treated cells.
• Despite initial differences, long-term Treg cell expansion, phenotype, and suppressor function were comparable between EVR and RAPA groups.

Conclusions:

• Everolimus (EVR) is feasible for expanding functionally competent Treg cells.
• These findings support the clinical application of EVR-expanded Treg cells in transplantation.