Experimental Treatment Allows Transplant Patients to Stop Taking Anti-Rejection Drugs

Three kidney transplant recipients at UCLA are living without the immunosuppressive medications that virtually every organ transplant patient in the world takes daily. They are part of a small but growing cohort — now numbering in the low dozens across several institutions — who have achieved what transplant medicine has pursued since the 1990s: immune tolerance, the state in which a recipient's body accepts a foreign organ as its own [1].

The results are real, but the context matters. The United States performed 48,149 organ transplants in 2024, a 3.3 percent increase over the prior year [2]. Nearly all of those patients will take anti-rejection drugs for the rest of their lives. The gap between three drug-free patients and 48,000 annual transplants defines the distance this science still needs to travel.

Source: OPTN/UNOS

Data as of Jan 1, 2025CSV

How Tolerance Induction Works

The concept behind transplant tolerance is straightforward even if the execution is not. Every protocol that has succeeded in humans relies on a biological phenomenon called chimerism — creating a state in which donor and recipient immune cells coexist in the same body [3].

At UCLA, Dr. Jeffrey Veale's team uses what they call a "delayed tolerance" approach. Months or years after a kidney transplant, the patient receives an infusion of blood stem cells collected from the original organ donor. These donor cells migrate to the recipient's bone marrow and integrate with the existing immune system, creating a mixed population of donor and recipient immune cells [1]. Over time, this mixed state teaches the recipient's immune system to recognize the transplanted kidney as "self" rather than foreign tissue. Patients are then gradually weaned off immunosuppressive drugs over a period of months [4].

The UCLA protocol is distinct because the stem cell infusion happens well after the transplant — a departure from earlier approaches that required both procedures to occur simultaneously. Of six patients treated in the Phase 1/2 trial, three are completely off immunosuppressive drugs, while the others are on reduced doses or actively tapering [1].

One of those patients, Karina Ledesma, received a kidney from her sister in October 2023 and a follow-up stem cell infusion in September 2024. By November 2024, she had stopped taking all immunosuppressive medications [4]. As of early 2026, the trial is expanding to accept patients who received transplants up to 20 years ago [1].

The Burden These Patients Escape

The drugs that transplant patients take — primarily tacrolimus and mycophenolate — suppress the immune system broadly, not selectively. This prevents organ rejection but exposes patients to a cascade of long-term side effects [5].

Infection rates are significantly elevated. One study found serious adverse infectious events in 35 percent of patients receiving the induction agent alemtuzumab, compared to 22 percent with basiliximab [6]. Cancer risk climbs over time: non-melanoma skin cancers affect nearly a quarter of liver transplant recipients, and rates of Kaposi's sarcoma and post-transplant lymphoproliferative disorder are more than three times the general population rate [6]. The drugs themselves can damage the transplanted kidney, sometimes necessitating a second transplant [7].

The financial toll compounds the medical one. Annual medication costs in the United States range from $10,000 to $14,000 per patient [8]. Medicare Part B covers immunosuppressive drugs for kidney recipients for only three years after transplant — a gap that contributes to medication non-adherence and, in some cases, organ loss [8]. Thirty-one percent of transplant recipients report that immunosuppressant expenses have had a moderate to severe adverse impact on their lives [9].

A Long History of Small Wins

UCLA's results did not emerge from nowhere. The pursuit of transplant tolerance through chimerism dates back nearly three decades, and the total number of patients enrolled in tolerance protocols worldwide remains remarkably small.

Source: Multiple sources

Data as of Jan 1, 2026CSV

The first clinical success came at Massachusetts General Hospital in 1998. A team led by David Sachs, Megan Sykes, Thomas Spitzer, and Tatsuo Kawai performed a combined kidney and bone marrow transplant on Janet McCourt, who received an HLA-matched organ from her sister [10]. McCourt has now lived without immunosuppressive drugs for over 25 years — the longest documented case of induced transplant tolerance [10].

MGH subsequently enrolled 10 subjects in trials of the protocol. Seven of ten achieved operational tolerance, defined as successful withdrawal of all immunosuppressive therapy for greater than one year [11]. Drug-free kidney survival in MGH trials has been documented for up to 17 years [10]. In 2023, a $25 million donation from Pablo and Almudena Legorreta established the Legorreta Center for Clinical Transplant Tolerance at MGH, the first center dedicated to this goal [10].

At Stanford, a separate approach using total lymphoid irradiation and anti-thymocyte globulin achieved similarly notable results. In a study of 29 fully HLA-matched kidney transplant recipients, 24 (83 percent) achieved complete immunosuppression withdrawal without subsequent rejection for at least two years after developing persistent mixed chimerism for six months or longer [12].

In the commercial sphere, Talaris Therapeutics developed FCR001, a stem cell therapy that achieved tolerance in 70 percent of kidney transplant patients in a Phase 2 study, with 26 of 36 recipients (72 percent) developing persistent chimerism and durably eliminating all immunosuppression [13]. However, the Phase 3 FREEDOM-1 trial was halted due to slow enrollment and excessive rates of graft-versus-host disease (GVHD) — a condition in which donor immune cells attack the recipient's tissues — among the first nine patients [14]. ImmunoFree, Inc. acquired Talaris's tolerance business in July 2023 and is now developing a redesigned product, IF001, for a new Phase 2 trial called RELIEF [14].

Source: OpenAlex

Data as of Jan 1, 2026CSV

How Long Is Long Enough?

The question transplant immunologists ask about these results is not whether patients can stop drugs — they clearly can — but whether tolerance will last. The field uses the term "operational tolerance" to describe drug-free graft survival, deliberately distinguishing it from proven permanent acceptance [3].

The threshold for confidence varies among researchers. Janet McCourt's 25-plus years at MGH provides the strongest evidence that durable tolerance is achievable [10]. But McCourt received her transplant from an HLA-identical sibling — an ideal immunological match that represents a small fraction of real-world transplants.

For the UCLA patients, the minimum follow-up is roughly 18 months for the earliest treated patient who stopped drugs. Transplant immunologists generally regard five years of drug-free survival as a meaningful benchmark, though even that threshold comes with caveats [3]. Among the first ten MGH patients, three had to resume immunosuppression due to chronic rejection or recurrence of native kidney disease, demonstrating that tolerance is not always permanent even when initially achieved [15].

The biological mechanisms that could undermine apparent tolerance are well-characterized. Memory T cells — immune cells that retain "memory" of previous immune encounters — can resist tolerance induction and reactivate years later [15]. Loss of chimerism, where donor cells gradually disappear from the recipient's bone marrow, has been documented and can precipitate rejection episodes. In early MGH trials, three of the first ten patients developed de novo donor-specific antibodies or acute rejection during a period researchers termed "chimerism transition syndrome," characterized by acute kidney injury during rapid immune reconstitution [15].

Funding, Interests, and Projected Costs

UCLA's expanded trial is supported by a $6.7 million grant from the California Institute for Regenerative Medicine (CIRM), a state agency funded by California taxpayer bonds [1]. The MGH Legorreta Center operates on its $25 million endowment [10]. The Stanford program has received funding through the National Institutes of Health and the Immune Tolerance Network [12].

On the commercial side, the trajectory of Talaris Therapeutics illustrates both the financial interest and the difficulty. Talaris raised $150 million in its 2021 IPO specifically to develop FCR001 for transplant tolerance [13]. After the FREEDOM-1 trial was discontinued, Talaris merged with Tourmaline Bio in October 2023, and ImmunoFree acquired the tolerance program [14]. ImmunoFree's scientific advisory board includes Dr. Robert Montgomery and Dr. Joseph Leventhal, both prominent transplant surgeons [14].

No company or institution has publicly disclosed a projected commercial price for tolerance induction therapy. The treatment involves collecting and processing donor stem cells, conditioning the recipient (which in some protocols requires low-dose radiation or chemotherapy agents), and extended follow-up monitoring. For context, a single kidney transplant in the United States costs approximately $260,000 [8]. If tolerance induction could eliminate $10,000–$14,000 in annual medication costs per patient, the lifetime savings for a patient who lives 20 years post-transplant would be $200,000–$280,000 — a figure that could justify a substantial upfront treatment cost.

Who Gets Left Out

Every tolerance protocol tested in humans to date shares a set of limitations that restrict who can benefit.

The most fundamental constraint is the donor requirement. All successful chimerism-based tolerance protocols require access to living donor cells — either collected at the time of transplant or obtained from the donor later [3]. Roughly 60 percent of kidney transplants in the United States use organs from deceased donors [16]. For these patients, tolerance induction through chimerism is not currently feasible unless the donor's bone marrow cells were banked at the time of organ recovery — a practice that is not standard [16].

HLA matching remains a significant factor. The Stanford protocol that achieved 83 percent success was limited to fully HLA-matched recipients — typically siblings [12]. The MGH program initially worked with HLA-matched pairs and has been gradually expanding to mismatched donors [10]. UCLA's CIRM-funded expansion aims to extend the protocol beyond well-matched sibling pairs, but this work is still early [1].

Patients with pre-existing sensitization — those who have already developed antibodies against donor tissue from prior transplants, blood transfusions, or pregnancies — face additional barriers. These patients' memory B and T cells are primed to attack donor tissue, making tolerance induction substantially harder [15].

Older transplant recipients occupy a complex position. Their immune systems are generally less reactive, reducing the risk of acute rejection but also potentially reducing the ability to establish robust chimerism [17]. No tolerance trial has specifically targeted elderly recipients.

Patients with autoimmune conditions present a theoretical concern: if their immune system is already dysregulated, the risk of unpredictable immune responses during tolerance induction may be higher, though this has not been formally studied in this context [3].

The cumulative effect of these exclusions is that the patients most likely to benefit from tolerance induction — young, healthy recipients of kidneys from HLA-matched living donors — represent a fraction of the transplant population. Extending tolerance to the broader population of transplant recipients, including those with deceased donor organs, mismatched HLA, and complex medical histories, remains an unsolved problem.

The Regulatory Road Ahead

Tolerance induction has been in clinical trials for over 25 years without reaching standard of care. The reasons are structural, not just scientific.

The FDA regulates cell therapies like stem cell infusions under its biologics framework, requiring Phase 1, 2, and 3 trials with safety and efficacy data [14]. Talaris's experience illustrates the challenge: its Phase 2 results were strong (72 percent durable chimerism), but the Phase 3 trial failed to enroll quickly enough and encountered safety signals (excessive GVHD) that led to discontinuation [13] [14].

Enrollment is inherently slow for these trials. Patients must have a willing living donor, meet HLA matching criteria, and consent to a protocol that involves conditioning agents with their own risks. The pool of eligible participants at any single institution is small [3].

The endpoint itself is unusual for FDA trials. Demonstrating that patients can safely stop taking drugs requires years of follow-up — not the weeks or months typical of pharmaceutical trials. A tolerance trial needs to show not just that drugs can be withdrawn, but that organs remain healthy for years afterward [3].

Given these constraints, researchers and industry observers do not expect tolerance induction to be available as a standard treatment before the early 2030s at the soonest, and only for kidney transplants from living donors [14]. Extension to liver, heart, and lung transplants — where the surgical complexity and immunological challenges differ — would follow later, if at all.

What This Means for 48,000 Annual Transplant Patients

The UCLA results, placed alongside the MGH and Stanford data, confirm that immune tolerance in organ transplantation is scientifically achievable. Patients can stop taking anti-rejection drugs. Some have done so for decades.

But the field has been in this position before. Early results generate justified excitement, small trials produce strong data, and then the transition to large-scale clinical practice stalls on enrollment challenges, safety signals, and the irreducible complexity of the human immune system.

The question is no longer whether tolerance works — the evidence from McCourt's 25-year case and dozens of others establishes that it does, at least in carefully selected patients. The question is whether it can be made to work reliably, safely, and affordably for the tens of thousands of transplant recipients who need it, including those with deceased donors, mismatched HLA types, and the full range of medical complexity that real-world patients present.

The gap between proof of concept and standard of care is where good ideas in medicine go to be tested most severely. Transplant tolerance has survived that test longer than most — and the coming years will determine whether it finally crosses the finish line or remains a remarkable achievement limited to the fortunate few.