编者按：燕赵汇贤才，十四载守初心。2026年8月21日，“第十四届陆道培血液病学术大会”于河北燕达陆道培医院盛大开幕。历经十四载学术积淀，本届大会聚焦造血干细胞移植、细胞免疫治疗、血液病精准诊疗等前沿议题，汇聚国内血液领域专家学者共探学科发展，是推动我国血液病诊疗事业进步的重要学术平台。会议期间，《肿瘤瞭望-血液时讯》特邀斯坦福大学血液和骨髓移植科主任Robert Negrin教授接受专访，围绕调节性T细胞（Treg）研究的里程碑事件、Orca-T疗法的临床突破意义、Treg技术平台的未来拓展方向等前沿话题分享专业见解。

《肿瘤瞭望-血液时讯》：您在本次大会的讲题是“Regulatory T Cells Come of Age”。您认为Treg研究发展至今，哪些里程碑事件标志着它真正“成熟”了？

Robert Negrin教授：我认为有两大标志性事件推动Treg领域研究走向成熟并获得广泛关注。第一是诺贝尔生理学或医学奖的授予，尤其表彰了Shimon Sakaguchi博士在调节性T细胞鉴定领域的贡献。他明确了Treg的细胞表型，为全球众多研究团队识别该细胞群奠定了核心基础。诺贝尔奖委员会也曾表示，授予该奖项的重要原因之一，是相信这一领域的研究将推动诸多医学领域的进步。

第二是基础研究向临床疗法的成功转化。由Orca BioSystems公司主导推进的相关疗法，基于临床前小鼠研究成果开发，并于今年6月30日获得美国食品药品监督管理局（FDA）批准。这是领域内第二个重要的分水岭时刻——源自基础科学的疗法成功应用于临床患者并被证实有效，获得了监管层面的正式认可。这两大事件是Treg研究发展历程中至关重要的突破。

Q1: Your lecture at this conference is titled "Regulatory T Cells Come of Age." In your view, what milestone events mark the true "coming of age" for Treg research to date?

I think there are really two major events that bring this research full circle and into the limelight. The first is the awarding of the Nobel Prize in Physiology or Medicine to three individuals, one in particular, Dr. Shimon Sakaguchi, who identified regulatory T cells. So he provided the phenotype that allowed investigators like our group and many other groups around the world to identify this cell population. Interestingly, the Nobel Prize committee stated that one of the reasons that they gave the Nobel Prize in this area is because they felt that there would be many medical advances that came from this work. So the second major event I believe is our work, led by the company Orca BioSystems, who translated the pre-clinical mouse data into a therapy that received FDA approval in the United States on June 30th of this year. So I think that's the second big watershed moment where a therapy that came from this fundamental science was brought to patients and shown to be effective and received regulatory approval at least in the United States for its use. So I believe those two events are really major findings in the last year.

《肿瘤瞭望-血液时讯》：近期Orca-T的III期研究显示，Treg联合输注显著降低了中重度慢性移植物抗宿主病（cGVHD），并改善了非复发死亡率（NRM）。作为Treg研究的奠基人之一，您如何看待这一临床突破的意义？

Robert Negrin教授：这一突破具有非常重要的临床价值，它证明我们能够进一步优化造血干细胞移植的疗效与安全性。传统造血干细胞移植的模式，是采集供体细胞后未做修饰直接回输，但移植物中的细胞成分复杂，部分细胞发挥治疗作用，部分细胞则可能带来损伤，最突出的危害就是导致非复发死亡——患者因治疗相关副作用不幸离世，这是非常惨痛的结局。Precision-T这项随机对照研究的核心成果之一，是将移植后的非复发死亡率降至仅3.4%。尽管仍有进一步优化的空间，但这已是非常显著的进步，大幅降低了移植治疗给患者带来的风险。我也期待这一突破能拓展移植的应用场景。例如，我们早已观察到，同时患有白血病与自身免疫病的患者，在移植成功后两种疾病均可得到缓解，但受限于移植风险，此前并未将移植用于单纯自身免疫病的治疗。如果能持续降低移植风险，该疗法不仅能使血液肿瘤患者明确获益，还有望拓展至更多疾病领域。

Q2: The recent Phase 3 study of Orca-T demonstrated that Treg-enriched adoptive transfer significantly reduced moderate-to-severe chronic GVHD (cGVHD) and improved non-relapse mortality (NRM). As one of the pioneers who laid the foundation for Treg-based research, how do you view the significance of this clinical breakthrough?

I think it's very significant because it showed that we can do better. And since the beginning of transplantation, the way we've done transplant is to collect the cells from the donor and infuse them without any modification. And it always seemed to me and I think to many people that could be improved upon, that we know that there are cells within that mix that are beneficial and then there are others that can cause harm. And the greatest harm that we see is what we call non-relapse mortality. That is that patients unfortunately can die from treatment-related effects. And that's the most devastating outcome.

So I think the Precision-T trial, the randomized trial, one of the major findings is that the non-relapse mortality was reduced to only 3.4%. Still room for improvement, but that's a major advance and that it reduces the risk that our patients must assume when they go through a transplant. And I hope that will allow us to use transplant in other settings, for example, in the treatment of severe autoimmune disorders where we know it works. We've known that for many years because of the observation that patients who have leukemia and an autoimmune disorder are both cured with a successful transplant. And we've never used transplant to treat other types of patients because of the risk. If we can reduce that risk, it has obvious implications for our cancer patients but also may extend this field into other areas.

《肿瘤瞭望-血液时讯》：Treg疗法已在III期试验中首次验证了疗效。您认为这一平台未来在血液病之外还有哪些拓展空间？下一步的关键挑战是什么？

Robert Negrin教授：这仅仅是Treg疗法发展的开端，如同所有科学进展一样，本次突破只是重要的一步。它的核心价值在于，首先证实了Treg细胞群的分离在技术上是可行的；其次证实了该细胞具有明确的临床价值，并且打通了监管审批的路径。在此基础上，目前已有大量关于细胞优化的探索方向，例如通过CAR修饰、其他创新策略增强Treg的功能与疗效。

未来，基于Treg的技术平台有望衍生出一系列创新疗法，适应症不仅覆盖血液肿瘤领域的更多疾病，也有望拓展至肿瘤领域之外的其他疾病。整体而言，Treg疗法的发展潜力巨大，后续的探索与优化将持续推动该领域的进步。

Q3: Treg therapy has now demonstrated efficacy for the first time in a Phase 3 trial. Beyond hematologic malignancies, what expansion opportunities do you foresee for this platform? And what are the key challenges ahead?

I think this is just the beginning. This is, like anything in science, another step. I think it's an important step because it establishes that these cell populations can be isolated. That's, from a technical perspective that you can do it. And second, that they have clinical value and they've been shown to have a regulatory pathway to approval at least in the United States and hopefully in other countries around the world.

Now there are many other ideas of how these cells can be modified, for example, with a CAR, or with various other strategies to improve their effects? And so I think hopefully we'll see a whole series of other approaches that are built upon this fundamental science and can treat a whole series of other disorders, in oncology but also I think outside of oncology.

专家简介

Robert Negrin 教授

斯坦福大学医学教授

曾于2000至2020年间担任血液与骨髓移植科主任。他本科毕业于加州大学伯克利分校，后获哈佛大学医学博士学位。在斯坦福大学完成内科学及血液学专科培训后，他于1990年加入教研团队。

其研究工作聚焦于细胞免疫学领域，重点探究动物模型及临床环境中移植物抗宿主反应与移植物抗肿瘤反应等复杂生物作用的深层机制。已发表300余篇原创论文、40篇专著章节并参与编纂一部专著。

曾获多项荣誉，包括Doris Duke杰出临床科学家奖，并当选美国医师协会会员。

曾担任国际细胞治疗学会主席及美国血液与骨髓移植学会主席

曾任《血液》期刊副主编并创办《血液进展》期刊

2025年就任美国血液学会候任主席，并于2026年正式担任主席职务。