October 25, 2024, Immune Tolerance
As kidney transplant recipients are aware, long-term use of triple immunosuppressants is standard practice following kidney transplantation to prevent rejection. However, prolonged use of immunosuppressants often leads to numerous adverse reactions, causing significant challenges. Reducing immunosuppressant dosages and inducing transplant tolerance have become critical challenges to address. Currently, new immunosuppressive regimens, novel immunosuppressants, and cell therapies are under development. Among these, cell therapy has garnered increasing attention. In-depth research on cell therapy offers a new avenue for the development of immunosuppressants, holding significant clinical importance.
Currently, a large-scale clinical trial is underway internationally, involving four types of regulatory T cells (Tregs), one regulatory macrophage (Mreg), and one tolerogenic dendritic cell for cell therapy. The study enrolled 104 adult patients who underwent living donor kidney transplants. In the control group, 66 patients—73% male, with a median age of 47 years—received standard immunosuppressive therapy, consisting of basiliximab, a steroid taper, mycophenolate mofetil, and tacrolimus. The cell therapy trial group included 38 patients—71% male, with a median age of 45 years—whose characteristics were matched to the control group. Their immunosuppressive therapy was similar but simplified (replacing basiliximab induction with cell therapy and gradually reducing mycophenolate mofetil), and they received one of six cell therapies. The results indicated that the incidence of biopsy-proven acute rejection in the control group receiving standard immunosuppressive therapy was 12% (within the expected range of 3.2–18.0). The overall incidence of acute rejection across the six parallel cell therapy trial groups was 16%. Fifteen (40%) patients who received cell therapy successfully discontinued mycophenolate mofetil and maintained only tacrolimus monotherapy. Compared to the control group, data on adverse events and the combined outcomes of acute rejection in all six cell therapy trial groups raised no safety concerns. Fewer infection events were reported in the cell therapy trial group compared to the control group.
This clinical study clearly demonstrates that regulatory cell therapy is both feasible and safe for living donor kidney transplant recipients, with fewer infectious complications but comparable rejection rates in the first year. Thus, immune cell therapy represents a promising treatment option for kidney transplant patients, potentially reducing reliance on conventional immunosuppressants. It is believed that, in the future, cell therapy will benefit more organ transplant patients, enhancing their quality of life post-transplantation.
References:
[1] Sawitzki, B., et al. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonized design and analysis of seven non-randomized, single-arm, phase 1/2A trials. Lancet, 2020. 395(10237): p. 1627–1639.
[2] Wood, K.J., Bushell, A., & Hester, J. Regulatory immune cells in transplantation. Nature Reviews Immunology, 2012. 12(6): p. 417–430.
Written by | Chen Juntao, Illustrations | Zou Garland
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