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Conrad Russell Y. Cruz, MD, PhD
Senior Editor, ISCT Telegraft
Children’s National Hospital
United States

ISCT Past President (2000-2002) Dr. Robert S. Negrin’s career as a physician–scientist helped us answer numerous questions about the biology of hematopoietic stem cell transplants. As a Professor of Medicine at Stanford University, where he led the Division of Blood and Marrow Transplantation for two decades, helped us understand graft-versus-host and graft-versus-tumor immune responses. Dr. Negrin’s long scientific career includes a publication resume of over 300 original research articles, 40 book chapters, and a book; awards like the Damon Runyon-Walter Winchell Cancer Fund Fellowship and the Doris Duke Distinguihed Clinical Scientist Award; service in peer reviewed journals like Blood and Blood Advances (where he served as the founding editor), and service to his fellow scientists. Besides being a past president of ISCT, he has served as president of American Society for Transplantation and Cellular Therapy (ASTCT, formerly ASMBT, in 2006), and is current President of the American Society of Hematology (ASH)¹.

Dr. Negrin’s path into this productive career began with a transformative encounter while studying as an undergraduate biochemistry major at the University of California, Berkeley.  He has described his early college years as a period when he was not quite sure of what to do. “I was a floundering undergraduate at UC Berkeley, and you can get lost at UC Berkeley, you can just go into the bowels of it and just be gone,” he recalls. “And I was going nowhere.” Interactions with one of his professors, future Nobel laureate Dr. Randy Schekman (2013 Nobel Prize winner for Physiology or Medicine with Dr. James Rothman and Dr. Thomas Südhof for work on cell membrane vesicle trafficking), helped convince him of a career in science. “He spent so much time with me, helping me find a lab, find a good thing, a good relationship. That was absolutely critical in my personal career and development. Without that, I'm not sure what would have happened,” he shares.

He then went on to earn his MD from Harvard Medical School (graduating cum laude in 1984) and then went to Stanford for a residency in internal medicine training and a fellowship in hematology/oncology. He would join the faculty in 1990 and has been with the institution ever since².

Over the next three decades, Dr. Negrin played a central role in building Stanford’s Blood and Marrow Transplantation (BMT) program into one of the most respected in the world, recognized not just for its clinical excellence, but for the fundamental immunology research it has put out¹.

His scientific trajectory has been marked by thoughtful pivots, which he frames as a critical  challenge. “The most challenging part is to know when you’re on a good trajectory, a good story, a good line of research versus a futile line of research,” he says.  An early focus on cytokine‑induced killer (CIK) cells—T cells with natural killer–like properties that could be expanded and kill tumor cells—progressed into clinical use but yielded uncertain benefits³.  “We probably inappropriately named [them] cytokine‑induced killer cells, as if that’s a different lineage,” he recalls, noting that the approach was “totally eclipsed by CAR T cells…much more specific, much more potent, much more effective,” and that he “probably stuck too long to that concept [of CIK cells] and should have pivoted earlier.”

The pivot toward regulatory T cells (Tregs) was catalyzed in part by his proximity to Dr. Samuel Strober, whom he says was a “great privilege” to have worked next door to, and who he believes “if he were alive, would have been on that short list for [the Nobel Prize].” The 2025 Nobel Prize for Physiology of Medicine was awarded to Dr. Mary Brunkow, Dr. Fred Ramsdell, and Dr. Shimon Sakaguchi for work related to immune tolerance. Together, Dr. Negrin’s and Dr. Strober’s groups showed that infusion of regulatory T cells could prevent graft‑versus‑host disease while retaining graft‑versus‑tumor effects. “It was just …so much more robust,” he says, emphasizing that the findings were reproducible across strains and laboratories and thus “more fundamental” to the field of transplantation than some of his earlier work.

Over subsequent years, Dr. Negrin made further inroads into regulatory T cell biology, and had the opportunity to translate these insights into the clinic. Reflecting on the challenges of moving things forward as therapies, Dr. Negrin says we need to recognize that we can’t always wait for the science to finish. “Clinical medicine is not perfect, [but] there's an urgency to it. We have patients in need, and we need to do better. And so,” he says, “we can't wait for something that's perfect.” 

A timely collaboration with Orca Bio, a biotechnology company developing allogeneic T cell immunotherapies, opened the door for such translational efforts. Dr. Negrin recognizes these partnerships are key, and academia cannot do it alone. “We’re good at discovery…[but] we’re not so good at process,” especially when robust, reproducible manufacturing must replace the lab’s tolerance for “throw it away, start over again” when experiments fail.  Crossing the “valley of death” from mouse to early‑phase human trials requires resources. 

“The big problem from academia is that we cannot generate the resources that it takes to move something forward, other than, you know, a single institutional maybe a phase one or early phase two trial, which we all know no one's going to accept, is really a definitive trial,” he says. “So, you know, if we're going to move it forward, we have to have a strategy that takes it out of academia.”

And for the regulatory T cell product specifically, “the reason I thought that was worthy of translation is because multiple labs were showing similar things.” He acknowledges that success also depends on cycles of capital, enthusiasm, and “luck” in finding aligned partners at the right time.

With Orca Bio, “we just found a fit,” he says. “They were able to do three things. [Number one], they raised a lot of money … the hundreds of millions of dollars it takes … Number two, they were able to develop a process that worked every time. And number three, they were able to export it so that it's not just a single institutional phase two trial.” 

These all culminated in phase 3 data and an FDA PDUFA date that, remarkably, was announced on the same day the Nobel Prize was awarded for the underlying basic science⁴.

Another of Dr. Negrin’s signature contributions arose from an interdisciplinary collaboration with Dr. Christopher Contag, leading to the in vivo bioluminescence imaging for tracking cells in mice that is now used in almost all translational research labs. He considers this work a signature contribution to the field. By engineering luciferase‑expressing cells and imaging them serially in intact animals, their group visualized immune cell trafficking, GVHD progression, and tumor responses over time, providing a dynamic view that traditional histology could not offer⁵.  “It's really exciting for me to see people use that all over the world,” he shares.  “I'm proud of and happy to see that people use it and benefit from it.”

Beyond his scientific contributions, Dr. Negrin’s mark on the field has extended through his leadership in professional societies. 

For ISCT specifically (formerly called the International Society for Hematotherapy and Graft Engineering/ISHAGE when he was president; in fact, he was part of the executive group that pushed for the change to ISCT), his presidency coincided with major standardization efforts that, in retrospect, seem almost routine but were transformative at the time.  ISCT coordinated an international effort to standardize CD34⁺ cell enumeration, which he describes as “a very important task to tackle” for a cell‑therapy society that otherwise had “no handle on what is the dose of cells we need to give” or a “standardized way to evaluate that across different centers.”  Using flow cytometry for clinical CD34⁺ assessment “was just not really very commonplace” then, he notes, so harmonizing reagents, gating strategies, and analyses across institutions was “a big international effort” that he considers “a very important contribution.” 

Also on the global stage, Dr. Negrin has long-standing volunteer work in Cambodia. Every year for close to fifteen years (with a brief pause during the pandemic), he has traveled to provide medical care in resource‑limited settings, working with a group of Cambodian professionals from Long Beach whose own histories reflect the country’s turbulent past.  “Every year, when I go back there, something absolutely profound happens,” he says. “I never know what it is…sometimes it’s about a patient…sometimes it’s an interaction with a student…but there’s always something.”  These trips have become a way for him to balance what he calls “the dumb lottery” of birth that leaves some with “enormous privilege” and others with “so little.” 

He has also worked to make these experiences reciprocal.  Through an American Society of Hematology visitor training program, he helped bring Cambodian physicians to Stanford for a four‑month visit, an experience that, in Phnom Penh, has become a defining professional credential for these visitors. 

Though mentorship has been a central theme in Dr. Negrin’s interactions with students, he does not particularly like the word “mentor,” preferring to think of trainees as colleagues, emphasizing the bidirectional nature of learning. His role is to help younger clinicians and scientists “figure out what they’re passionate about” and when to pivot from unproductive lines of work. He is particularly proud of the privilege of “training a lot of young people from all over the world” and then watching them return to their communities with new skills and perspectives.

For Dr. Negrin, professional societies are crucial in sustaining morale and purpose during what he calls “a frustrating and disillusioned time.”  “We become kind of cynical,” he says, “and we need things to bring us together, to celebrate us as a community…to be inspired by each other.”

ISCT’s international meetings, for example, has helped broaden his understanding of research elsewhere. “That's what these societies do best, the meetings that they hold … the ideas they bring together, the people they bring together from all over the world … it's just very eye opening, I think, for all of us to sort of see … there's people all over the world that are studying these problems, and they have different challenges, and they have different successes, and they have different perspectives, and they have different ways of doing things,” he says. “And we can all learn from that and benefit from that, and yet, and on top of that, you know, meet wonderful people that are and have a lot of fun. So I think these societies are incredibly important to provide that environment, especially now when … it's easy to become sort of disengaged. It’s important to say: wait a minute, there's a community here … of like minded people that inspires us.”

Professional societies also have a role to play in public engagement, to stem the tide of public skepticism towards science. “Obviously it’s become apparent we need to explain ourselves,” he says. “We can’t just assume that because we think it’s worthwhile that the rest of society is going to agree with us.” He thinks that societies like ISCT must engage more deliberately with the public and with policymakers.

Looking forward, Dr. Negrin has contemplated writing a book that talks about his experience in science and medicine, and his reflections on the courage of patients, his gratitude, and the meaning he found in this work. Whether through such a book or through continued scientific and clinical leadership, his career has been defined by a willingness to pivot when “a better idea came along,” a candid acknowledgment of the role of luck, and a sustained insistence that, even in difficult times, “it’s absolutely worth it” to devote a life to advancing science for the common good.

We told him we’d be lining up to have him sign our copies of this book! 

REFERENCES

1. https://profiles.stanford.edu/robert-negrin
2. https://cap.stanford.edu/profiles/viewBiosketch?facultyId=4138&name=Robert_Negrin
3. Laport GG, Sheehan K, Baker J, Armstrong R, Wong RM, Lowsky R, Johnston LJ, Shizuru JA, Miklos D, Arai S, Benjamin JE, Weng WK, Negrin RS. Adoptive immunotherapy with cytokine-induced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011 Nov;17(11):1679-87. doi: 10.1016/j.bbmt.2011.05.012. Epub 2011 May 25. PMID: 21664472; PMCID: PMC3175285.
4. https://orcabio.com/orca-bio-announces-fda-acceptance-and-priority-review-of-the-biologics-license-application-bla-for-orca-t-to-treat-hematological-malignancies/
5. Negrin RS, Contag CH. In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease. Nat Rev Immunol. 2006 Jun;6(6):484-90. doi: 10.1038/nri1879. PMID: 16724101.