New method to minimize immunosuppression after organ transplantation
5 hours ago
- A novel clinical strategy combining solid organ transplantation (SOT) with non-myeloablative conditioning and naïve T-cell-depleted hematopoietic stem cell transplantation (HSCT) plus memory T-cell infusions is presented.
- In two high-risk patients (a multivisceral recipient with full HLA mismatch and a hypersensitized kidney recipient with prior graft rejections), this approach induced transient mixed chimerism and allowed sustained minimal immunosuppression (monotherapy) with no graft rejection for over five years.
- Mixed lymphocyte reaction (MLR) tests showed recipient cells were hyporesponsive to donor and third-party cells but retained reactivity to CMV, indicating preserved antiviral immunity.
- TCRβ deep sequencing identified donor-reactive T-cell clonotypes pre-HSCT that were undetectable post-transplant, suggesting elimination of alloreactive clones.
- The protocol was safe, with no graft-versus-host disease or severe infections, and has led to an ongoing phase I clinical trial (NCT06997471) to test this approach in more patients.