| Antigen targeted CAR Treg + CD25 - biased low dose IL-2 to enable Calcineurin inhibition minimization after living-donor kidney transplantation |
| Paper ID : 1321-IGA |
| Authors |
|
salma yalouh * University of Birmingham |
| Abstract |
| Background and Aim: The persistent high use of CNIs in preventing allograft rejection can lead to impaired Treg function and unstable FOXP3 expression putting the patient at higher risk of nephrotoxicity, infection, and potential malignancy. This paper proposes a theoretical model of LD-IL-2 conditioning of engineered anti HLA-A2 CAR Tregs to allow localized immunosuppression and prevent CNI toxicity Materials and Methods: isolation and transduction of CD4+ CD25^hi^FOXP3+ Tregs with an anti HLA-A2 CAR construct containing CD28/CD3 costimulatory domains to promote CD25 (IL-2R) signaling. After transduction, the CAR Tregs will be cultured in LD-IL-2 to stimulate exogenous cytokine support under CNI induced IL-2 depletion. Theoretical assessment of phenotypic stability to confirm CAR Treg function and stability. Results: IL-2 conditioning is expected to maintain FOXP3+ stability and enhance CAR Treg persistence to show stronger suppression of HLA-A2 Teff proliferation and cytokine leakage. In transplant settings, this approach may increase Treg: Tconv ratios, reduce serum IL-6 and IFN-y and improve graft histology and renal function Conclusion: This proposed model offers a feasible and mechanistically grounded approach to minimize CNI usage while preserving graft tolerance. Furthermore, it highlights a potential shift toward precision immunomodulation, where cytokine guided cellular therapies maintain long term immune balance with reduced system toxicity. |
| Keywords |
| CAR Tregs, low-dose IL-2, calcineurin inhibitors, immune tolerance, and kidney transplantation. |
| Status: Accepted |
