March 2026

ORGAN TRANSPLANT

ADVANCING IMMUNE TOLERANCE IN ORGAN TRANSPLANTATION

Featuring: Joseph R. Leventhal, MD, PhD

For decades, through a series of clinical trials, Northwestern Medicine is pioneering innovative approaches in kidney transplantation to achieve immune tolerance and significantly reduce reliance on lifelong immunosuppression.

One trial investigated how a one-time infusion of donor-derived hematopoietic stem cells alongside the transplanted organ can lead to chimerism in living-donor kidney recipients. The trial enabled 26 of 37 patients to withdrawal from conventional immunosuppressive drugs within one-year post-transplant. In 2026, with more than 16 years of follow up, all 16 patients have maintained stable graft function with fewer side effects, and they report higher quality of life than patients maintained on conventional immunosuppressive drugs.

This and other protocols are being led by Joseph R. Leventhal, MD, PhD. While standard immunosuppressants are effective early post-transplant, their long-term side effects, including nephrotoxicity, infection risk and metabolic complications, impair both graft longevity and patient quality of life. Cellular therapy offers the potential to preserve graft function without these drug-related toxicities.

As more patients successfully taper off immunosuppressants with stable graft outcomes, experts see this approach expanding to deceased-donor recipients, other solid organs and being the shift toward personalized, cellular immune modulation in transplant medicine.
 
Active Tolerance Trials at Northwestern Medicine

TLI, TBI, ATG & Hematopoietic Stem Cell Transplantation and Recipient T Regs Therapy in Living Donor Kidney Transplantation
Principal investigator: Joseph Leventhal, MD, PhD

This is a dose-escalation phase 1b trial to test infusing recipient-purified Tregs in patients following combined living donor kidney and hematopoietic stem cell transplantation.

It is a single-group, one-arm, open, nonrandomized study.
 
Regulatory T Cell Therapy to Achieve Immunosuppression REduction (RETIRE)
Principal Investigator: Mohammed Javeed I. Ansari, MD

This is a prospective, multi-national, multi-center, open-label, randomized phase 2 trial. Subjects with end-stage renal disease undergoing a living donor kidney transplant will be enrolled and initially randomized to either arm 1 or arm 2:
  • Arm 1 SOC: Standard of care immunosuppression (N=14)
  • Arm 2 TRACT/MONO: TRK-001 and initial SOC immunosuppression weaned to achieve monotherapy (N=20)

In the third month post-transplant, arm 2 subjects will be further randomized before weaning to achieve either mTOR or CNI monotherapy as follows:
  • Arm 2A: TRACT/MONO mTOR (N=10) or
  • Arm 2B: TRACT/MONO CNI (N=10)

All subjects will be followed for five years post-transplant, which will include a two-year post-transplant follow-up period and a three-year surveillance period.
 
ECP-DL Cell Infusion for Induction in Living Donor Kidney (LDK) Transplants (ECP)
Principal Investigator: Joseph Leventhal, MD, PhD

This is an open label, single-center (multi-site, for the purposes of an external sub-I collaborator) phase 1 study of ECP-DL in living donor renal transplant recipients. The safety portion of this study will continue for one year, but the patients will be followed for up to two years. Participants will receive standard of care immune suppression without antibody induction (thymoglobulin or simulect) before living donor kidney transplantation.

Following the ECP-DL infusion and before the kidney transplant (day -2), blood will be collected for immunophenotypic analysis of circulating leukocytes by flow cytometry, as well as functional immune assays to assess for donor specific hypo-responsiveness (DSA quantification).

Dose escalation of ECP-DL will be based upon the absence of infusion-related side effects and specific adverse events (subsequent rejection episodes, allosensitization, development of opportunistic infection) with at least two months before escalating to the next dosing tier.

Transplant will be delayed in any patient with circulating de novo donor-specific antibodies identified for a minimum of 30 days while another donor search is performed for one lacking the same HLA-antigens. 

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Joseph R. Leventhal, MD, PhD, Fowler McCormick Professor of Surgery, Director of Kidney and Pancreas Transplant

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