Editor’s Note: In the height of summer, Harbin—known as the “Ice City”—welcomed a gathering of scientific minds. From July 11 to 13, 2025, the 9th Annual Hematologic Oncology Congress of the Chinese Society of Clinical Oncology (CSCO) was held in Harbin. The congress brought together top experts from China and abroad to discuss advancements in leukemia, lymphoma, multiple myeloma, and other hematologic diseases, spanning basic research, novel drug development, precision medicine, and clinical translation. Acute myeloid leukemia (AML) remains one of the most challenging diseases in clinical hematology, urgently requiring innovative breakthroughs. At the conference, Professor Xiaoyu Zhu from the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) presented exciting findings on “Basic and Translational Research on Double-Negative T Cells for AML Treatment.” In an exclusive interview with Oncology Frontier – Hematology Frontier, Professor Zhu further elaborated on the latest progress in this cutting-edge field.Oncology Frontier – Hematology Frontier: In recent years, double-negative T cells (DNTs) have garnered growing attention in the treatment of AML. Could you share the latest developments in basic research on DNTs and their therapeutic potential for AML?
Professor Xiaoyu Zhu: Double-negative T cells (DNTs) are a relatively rare T cell subset, accounting for only 1% to 5% of peripheral blood lymphocytes. Due to current technical limitations in their isolation and expansion, basic research on DNTs remains limited. Most of the foundational work has come from the team led by Professor Li Zhang at the University of Toronto in Canada. Their in vitro studies demonstrated that DNTs exhibit cytotoxic activity against AML. Additionally, they validated in mouse models that DNTs not only possess anti-AML activity but also suppress graft-versus-host disease (GVHD). These findings suggest that DNTs are an ideal model for cell therapy, capable of separating GVHD from graft-versus-leukemia (GVL) effects.
Our center has also been actively conducting DNT-related studies, including in vitro experiments, animal studies, and clinical trials. In vitro, we found that DNTs can effectively kill both AML cell lines and primary AML cells, although responses vary among patients. To address this variability, we identified several potential molecular markers to predict DNT cytotoxicity and are now working to validate these findings.
In GVHD models, DNTs also demonstrated an inhibitory effect—particularly by suppressing the proliferation of CD4+ and CD8+ T cells. In animal models, we confirmed that DNTs significantly reduced GVHD incidence. Building on this, we moved into clinical research.
Our first clinical trial focused on DNT therapy in patients who relapsed after AML transplantation—marking the first-ever clinical use of DNTs in humans. We enrolled 10 patients, a population that typically has poor prognosis after relapse. Encouragingly, following DNT infusion, the overall survival rate reached 40%, and four patients remain disease-free five years later.
Recently, we also completed and published a Phase I clinical trial aimed at preventing post-transplant AML relapse. Six patients were enrolled, and the one-year survival rate was approximately 88%. These promising results provide compelling clinical evidence supporting the use of DNTs in AML therapy, and point toward their potential as a novel and effective treatment option for this high-risk patient population.
Oncology Frontier – Hematology Frontier: Given the unique advantages that double-negative T cells (DNTs) have shown in AML treatment, what innovative strategies or future applications do you believe could further unlock their therapeutic potential?
Professor Xiaoyu Zhu: Acute myeloid leukemia (AML) is the most common form of leukemia in adults. It is highly heterogeneous and carries a high risk of relapse and treatment resistance. Compared to acute lymphoblastic leukemia (ALL), progress in immune cell therapy for AML has been relatively slow. However, the emergence of DNTs is beginning to bring meaningful breakthroughs to this area. DNTs not only possess anti-AML activity but also exhibit a favorable safety profile by effectively suppressing graft-versus-host disease (GVHD).
To fully harness the potential of DNTs in AML therapy, several strategies can be pursued: First, we must focus on the precise identification of AML patient subgroups that are most likely to benefit from DNT therapy. This is especially important for high-risk patients who are prone to relapse and are not eligible for transplantation. For these individuals, DNT infusion may significantly improve survival outcomes.
Second, the development of CAR-DNTs represents a promising direction. Unlike traditional universal CAR-T cells, which require complex genetic engineering of T cells, CAR-DNTs can be used directly without genetic modification, making them a true off-the-shelf cell therapy product. This innovation significantly reduces the cost and complexity of treatment while expanding the scope of DNTs in various therapeutic settings. As such, CAR-DNTs hold great promise as a next-generation approach in the field of immunotherapy.
These advancements may pave the way for DNT-based therapies to play a major role in the future of AML treatment and beyond.
Professor Xiaoyu Zhu The First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital)
· MD, Chief Physician, Doctoral and Postdoctoral Supervisor
· Director of the Department of Hematology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
· Deputy Director, Institute of Hematology and Cell Therapy, University of Science and Technology of China
· Discipline Leader of the National Clinical Key Specialty Construction Program
· Director, Anhui Provincial Hematology Quality Control Center
· Reserve Talent for Academic and Technical Leaders of Anhui Province
· Recipient, Anhui Provincial Outstanding Youth Fund
· Honoree, “Most Beautiful Science and Technology Worker” in Anhui Province
· Leading Talent of the 9th Batch “Special Support Plan” for Health Innovation in Anhui Province
· Team Leader, Outstanding Scientific Innovation Team for “Cord Blood Transplantation in Malignant Hematologic Diseases,” Anhui Province
Academic and Professional Roles:
· Member, 5th Committee of the Hematology Physician Branch, Chinese Medical Doctor Association
· Deputy Leader, Aplastic Anemia Collaboration Group, Hematology Specialty Alliance of China
· Member, Hematopoietic Stem Cell Transplantation Group, Hematology Branch, Chinese Medical Association
· Vice Chair, 8th Committee of the Anhui Hematology Society
· Member, 9th and 10th Youth Committees, Hematology Branch, Chinese Medical Association
Scientific Contributions:
· Principal Investigator of four National Natural Science Foundation projects and six provincial/ministerial-level grants
· Published over 30 SCI papers as corresponding or co-corresponding author in leading journals such as Cell, Blood, Cell Reports, Cell Reports Medicine, Advanced Functional Materials, Bioactive Materials, American Journal of Hematology, and Blood Advances
· Chief editor of the monograph “Cord Blood Transplantation: Basics and Clinical Applications”
Editor’s Note: In the height of summer, Harbin—known as the “Ice City”—welcomed a gathering of scientific minds. From July 11 to 13, 2025, the 9th Annual Hematologic Oncology Congress of the Chinese Society of Clinical Oncology (CSCO) was held in Harbin. The congress brought together top experts from China and abroad to discuss advancements in leukemia, lymphoma, multiple myeloma, and other hematologic diseases, spanning basic research, novel drug development, precision medicine, and clinical translation. Acute myeloid leukemia (AML) remains one of the most challenging diseases in clinical hematology, urgently requiring innovative breakthroughs. At the conference, Professor Xiaoyu Zhu from the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) presented exciting findings on “Basic and Translational Research on Double-Negative T Cells for AML Treatment.” In an exclusive interview with Oncology Frontier – Hematology Frontier, Professor Zhu further elaborated on the latest progress in this cutting-edge field.Oncology Frontier – Hematology Frontier: In recent years, double-negative T cells (DNTs) have garnered growing attention in the treatment of AML. Could you share the latest developments in basic research on DNTs and their therapeutic potential for AML?
Professor Xiaoyu Zhu: Double-negative T cells (DNTs) are a relatively rare T cell subset, accounting for only 1% to 5% of peripheral blood lymphocytes. Due to current technical limitations in their isolation and expansion, basic research on DNTs remains limited. Most of the foundational work has come from the team led by Professor Li Zhang at the University of Toronto in Canada. Their in vitro studies demonstrated that DNTs exhibit cytotoxic activity against AML. Additionally, they validated in mouse models that DNTs not only possess anti-AML activity but also suppress graft-versus-host disease (GVHD). These findings suggest that DNTs are an ideal model for cell therapy, capable of separating GVHD from graft-versus-leukemia (GVL) effects.
Our center has also been actively conducting DNT-related studies, including in vitro experiments, animal studies, and clinical trials. In vitro, we found that DNTs can effectively kill both AML cell lines and primary AML cells, although responses vary among patients. To address this variability, we identified several potential molecular markers to predict DNT cytotoxicity and are now working to validate these findings.
In GVHD models, DNTs also demonstrated an inhibitory effect—particularly by suppressing the proliferation of CD4+ and CD8+ T cells. In animal models, we confirmed that DNTs significantly reduced GVHD incidence. Building on this, we moved into clinical research.
Our first clinical trial focused on DNT therapy in patients who relapsed after AML transplantation—marking the first-ever clinical use of DNTs in humans. We enrolled 10 patients, a population that typically has poor prognosis after relapse. Encouragingly, following DNT infusion, the overall survival rate reached 40%, and four patients remain disease-free five years later.
Recently, we also completed and published a Phase I clinical trial aimed at preventing post-transplant AML relapse. Six patients were enrolled, and the one-year survival rate was approximately 88%. These promising results provide compelling clinical evidence supporting the use of DNTs in AML therapy, and point toward their potential as a novel and effective treatment option for this high-risk patient population.
Oncology Frontier – Hematology Frontier: Given the unique advantages that double-negative T cells (DNTs) have shown in AML treatment, what innovative strategies or future applications do you believe could further unlock their therapeutic potential?
Professor Xiaoyu Zhu: Acute myeloid leukemia (AML) is the most common form of leukemia in adults. It is highly heterogeneous and carries a high risk of relapse and treatment resistance. Compared to acute lymphoblastic leukemia (ALL), progress in immune cell therapy for AML has been relatively slow. However, the emergence of DNTs is beginning to bring meaningful breakthroughs to this area. DNTs not only possess anti-AML activity but also exhibit a favorable safety profile by effectively suppressing graft-versus-host disease (GVHD).
To fully harness the potential of DNTs in AML therapy, several strategies can be pursued: First, we must focus on the precise identification of AML patient subgroups that are most likely to benefit from DNT therapy. This is especially important for high-risk patients who are prone to relapse and are not eligible for transplantation. For these individuals, DNT infusion may significantly improve survival outcomes.
Second, the development of CAR-DNTs represents a promising direction. Unlike traditional universal CAR-T cells, which require complex genetic engineering of T cells, CAR-DNTs can be used directly without genetic modification, making them a true off-the-shelf cell therapy product. This innovation significantly reduces the cost and complexity of treatment while expanding the scope of DNTs in various therapeutic settings. As such, CAR-DNTs hold great promise as a next-generation approach in the field of immunotherapy.
These advancements may pave the way for DNT-based therapies to play a major role in the future of AML treatment and beyond.
Professor Xiaoyu Zhu The First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital)
· MD, Chief Physician, Doctoral and Postdoctoral Supervisor
· Director of the Department of Hematology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
· Deputy Director, Institute of Hematology and Cell Therapy, University of Science and Technology of China
· Discipline Leader of the National Clinical Key Specialty Construction Program
· Director, Anhui Provincial Hematology Quality Control Center
· Reserve Talent for Academic and Technical Leaders of Anhui Province
· Recipient, Anhui Provincial Outstanding Youth Fund
· Honoree, “Most Beautiful Science and Technology Worker” in Anhui Province
· Leading Talent of the 9th Batch “Special Support Plan” for Health Innovation in Anhui Province
· Team Leader, Outstanding Scientific Innovation Team for “Cord Blood Transplantation in Malignant Hematologic Diseases,” Anhui Province
Academic and Professional Roles:
· Member, 5th Committee of the Hematology Physician Branch, Chinese Medical Doctor Association
· Deputy Leader, Aplastic Anemia Collaboration Group, Hematology Specialty Alliance of China
· Member, Hematopoietic Stem Cell Transplantation Group, Hematology Branch, Chinese Medical Association
· Vice Chair, 8th Committee of the Anhui Hematology Society
· Member, 9th and 10th Youth Committees, Hematology Branch, Chinese Medical Association
Scientific Contributions:
· Principal Investigator of four National Natural Science Foundation projects and six provincial/ministerial-level grants
· Published over 30 SCI papers as corresponding or co-corresponding author in leading journals such as Cell, Blood, Cell Reports, Cell Reports Medicine, Advanced Functional Materials, Bioactive Materials, American Journal of Hematology, and Blood Advances
· Chief editor of the monograph “Cord Blood Transplantation: Basics and Clinical Applications”
