编者按：2025年10月31日，由北京大学人民医院雄安医工交叉转化研究院主办，国家血液系统疾病临床医学研究中心-北京大学血液病研究所承办的“2025国际细胞治疗及生物医学前沿大会”在河北雄安盛大召开。会上，加州大学尔湾分校Stefan O. Ciurea教授分享了《Adoptive NK Cell Therapy Before and After Transplantation for AML》（急性髓系白血病移植前后的过继性NK细胞疗法）的精彩内容，为高度难治性急性髓系白血病移植患者提供全新治疗策略与希望。《肿瘤瞭望-血液时讯》现场特邀Stefan O. Ciurea教授接受采访，分享过继细胞治疗在造血干细胞移植中的应用现状、面临的关键挑战及未来发展方向。

《肿瘤瞭望-血液时讯》：随着造血干细胞移植技术的不断进步，过继细胞治疗作为一种增强免疫功能的策略，在改善患者预后方面展现了巨大的潜力。您能分享一下过继细胞治疗在移植后的应用现状及其临床优势吗？

Stefan O. Ciurea教授：我们团队重点聚焦于NK细胞的研究，以期降低移植后疾病复发风险。Ⅱ期临床试验显示，移植后接受NK细胞治疗的患者复发率近乎为零，明显优于未接受NK细胞治疗的患者。基于此，我们计划开展随机对照研究，以进一步评估NK细胞在移植患者中的临床获益。此外，我们还将该疗法应用于高度难治性急性髓系白血病患者，总体应答率约50%，包括完全缓解（CR）或CR伴不完全血液学恢复（CRi），其中约40%患者成功桥接移植并实现长期生存。

移植后细胞治疗的另一重要方向是减少主要感染并发症，尤其是病毒感染。我们团队重点研究BK病毒特异性T细胞，用于治疗移植后出现BK病毒性膀胱炎或肾炎的患者，并计划在加利福尼亚开展Ⅱ期多中心研究，针对接受干细胞及实体器官移植后出现相关并发症的患者。其他研究团队也在开发针对CMV、EBV等病毒的特异性T细胞疗法。

这些研究有望在未来显著降低移植相关并发症的发生率，提升治疗效果，并减少治疗相关死亡率。同时，NK细胞干预有望解决移植后疾病复发这一长期未能突破的关键问题。总之，期待NK细胞在未来能够真正带来突破。

Oncology Frontier-Hematology Frontier：With the continuous advancement of hematopoietic stem cell transplantation (HSCT technology), adoptive cellular therapy has shown great potential in enhancing immune function and improving patient outcomes. Could you share the current status of adoptive cellular therapy post-transplant and its clinical advantages?

Prof. Stefan O. Ciurea：Our team has been focusing on NK cell research with the aim of reducing the risk of disease relapse after transplantation. Phase II clinical trials have shown that the relapse rate in patients receiving NK cell therapy post-transplantation is nearly zero, significantly better than in those who did not receive NK cells. Based on these results, we plan to conduct a randomized controlled study to further evaluate the clinical benefits of NK cells in transplant recipients. In addition, we have applied this therapy to patients with highly refractory acute myeloid leukemia, achieving an overall response rate of approximately 50%, including complete remission (CR) or CR with incomplete hematologic recovery (CRi). About 40% of these patients successfully bridged to transplantation and achieved long-term survival.

Another important focus of post-transplant cell therapy is the prevention and management of infectious complications, particularly viral infections. Our team has been studying BK virus-specific T cells to treat patients who develop BK virus-associated cystitis or nephritis after transplantation, and we plan to conduct a Phase II multicenter study in California targeting patients who develop such complications after receiving stem cell or solid organ transplants. Other research teams are also developing virus-specific T cell therapies against CMV, EBV, and other viruses.

These studies are expected to significantly reduce the incidence of transplant-related complications in the future, improve treatment outcomes, and decrease treatment-related mortality. At the same time, NK cell intervention has the potential to address post-transplant disease relapse, a critical issue that has not yet been overcome. Overall, NK cell therapy is expected to bring a true breakthrough in the future.

《肿瘤瞭望-血液时讯》：在造血干细胞移植后，如何选择合适的过继细胞治疗方案以最大化提高免疫重建效果？目前临床中面临的主要挑战是什么，如何应对这些挑战以优化疗效？

Stefan O. Ciurea教授：移植的主要问题在于免疫重建延迟，这会增加治疗相关死亡率，提高移植后疾病复发的风险。长期以来，加速免疫重建一直是移植领域的重要研究目标。为此，我们正在探索一种移植后细胞疗法，以加速免疫重建。同时，如前所述，开发病毒特异性T细胞有助于治疗移植患者因严重免疫缺陷而发生的并发症。我们希望首先是控制这些病毒的活性，理想情况下，可进一步改善整体免疫重建，防止病毒再激活及相关并发症的发生。

Oncology Frontier-Hematology Frontier：After hematopoietic stem cell transplantation, how do you select the appropriate adoptive cellular therapy approach to maximize immune reconstitution? What are the main challenges faced in clinical practice, and how can these challenges be addressed to optimize efficacy?

Prof. Stefan O. Ciurea：The main challenge in transplantation lies in delayed immune reconstitution, which increases treatment-related mortality and elevates the risk of disease relapse post-transplant. Accelerating immune reconstitution has long been an important research goal in the field of transplantation. To address this, we are exploring a post-transplant cellular therapy aimed at promoting immune recovery. In parallel, as previously mentioned, the development of virus-specific T cells can help manage complications arising from severe immune deficiency in transplant recipients. The initial objective is to control viral activity, and ideally, to further enhance overall immune reconstitution, thereby preventing viral reactivation and associated complications.

《肿瘤瞭望-血液时讯》：过继细胞治疗在治疗移植相关并发症（如移植物抗宿主病）中发挥了重要作用。您认为未来在该领域的创新研究重点应集中在哪些方面？哪些新兴技术或策略有望进一步提高治疗效果？

Stefan O. Ciurea教授：移植过程中，移植物抗宿主病（GVHD）历来是主要并发症之一。然而，在GVHD预防方面已取得显著进展。我们团队专注于GVHD的预防而非治疗，通过在移植后前三个月应用新型类固醇布地奈德（Entocort），在预防严重胃肠道GVHD方面取得了显著成效。相关研究成果已发表于American Journal of Hematology。

此外，研究显示，NK细胞在移植后不会引发GVHD，病毒特异性T细胞引起严重GVHD的情况也极为罕见。这类细胞疗法主要针对病毒，具有低水平的同种异体反应性，从而显著降低GVHD发生率。总体来看，基于现有研究结果，GVHD在移植后已不再构成主要障碍，而这些新型细胞疗法引发严重GVHD的可能性极低。

Oncology Frontier-Hematology Frontier：Adoptive cellular therapy plays an important role in managing transplant-related complications, such as graft-versus-host disease (GVHD). What do you think should be the focus of future innovative research in this field? Which emerging technologies or strategies are likely to further improve treatment outcomes?

Prof. Stefan O. Ciurea：Graft-versus-host disease (GVHD) has historically been one of the major complications in transplantation. However, significant progress has been made in GVHD prevention. Our team has focused on prevention rather than treatment, achieving notable success in preventing severe gastrointestinal GVHD by administering the novel steroid budesonide (Entocort) during the first three months post-transplant. The results of this research have been published in the American Journal of Hematology.

Furthermore, studies have shown that NK cells do not induce GVHD after transplantation, and the occurrence of severe GVHD caused by virus-specific T cells is extremely rare. These cellular therapies are primarily targeted against viruses and exhibit low alloreactivity, thereby significantly reducing the incidence of GVHD. Overall, based on current research, GVHD no longer represents a major obstacle post-transplant, and the likelihood of severe GVHD induced by these novel cellular therapies is minimal.

Stefan O. Ciurea教授现场作报告

专家简介

Stefan O. Ciurea 教授

加州大学尔湾分校

Stefan O. Ciurea博士是加州大学尔湾分校健康系统（UCI Health）血液学家，同时担任 Chao Family 综合癌症中心造血干细胞移植与细胞治疗项目主任。

Ciurea博士在罗马尼亚雅西的Grigore T. Popa医药大学获得医学学位，并在宾夕法尼亚州哈里斯堡的UPMC Pinnacle Harrisburg完成内科住院医师培训。随后，他在伊利诺伊大学芝加哥医学院完成血液肿瘤学奖学金培训，并在德克萨斯大学MD安德森癌症中心完成干细胞移植与细胞治疗奖学金培训。

加入Chao Family综合癌症中心之前，Ciurea博士在MD安德森癌症中心干细胞移植与细胞治疗系任教超过十年。

他已发表150余篇同行评审文章，并撰写10多篇书籍章节。同时，他担任多项临床试验的首席研究员，包括研究者发起的试验。Ciurea博士曾受邀在全球50多个学术会议上发表演讲，其中包括主旨报告。