Prophylactic infusion of allogeneic double-negative T cells as immune modulators to prevent relapse in high-risk AML patients post-Allo-HSCT: a phase I trial

Prophylactic infusion of allogeneic double-negative T cells as immune modulators to prevent relapse in high-risk AML patients post-Allo-HSCT: a phase I trial

Abstract Relapse remains a major challenge for high-risk acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our first-in-human Phase I trial (ChiCTR-1900022795), we have demonstrated that third-party donor-derived double-negative T cell...

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Main Authors: Guangyu Sun, Xingchi Chen, Tianzhong Pan, Kaidi Song, Haicun Xie, Meijuan Tu, Xiang Wan, Wen Yao, Yaxin Cheng, Ziwei Zhou, Dongyao Wang, Yongsheng Han, Baolin Tang, Liming Yang, Xiaoyu Zhu
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Experimental Hematology & Oncology
Subjects:
Double negative T cell
Acute myeloid leukemia
Allogeneic hematopoietic stem cell transplantation
Relapse
Adoptive cellular therapy
Immune modulator
Online Access:https://doi.org/10.1186/s40164-025-00680-1
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Summary:Abstract Relapse remains a major challenge for high-risk acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our first-in-human Phase I trial (ChiCTR-1900022795), we have demonstrated that third-party donor-derived double-negative T cells (DNTs) are safe and effective for treating relapsed AML. This Phase I study aims to further evaluate the safety and efficacy of allo-DNTs in preventing relapse in AML patients post-allo-HSCT. Six high-risk AML patients received three infusions of off-the-shelf allo-DNTs at one-month intervals, administered 60 to 100 days post-allo-HSCT without lymphodepleting chemotherapy. No dose-limiting toxicity, DNT-related graft-versus-host disease (GvHD), or severe cytokine release syndrome (CRS) occurred. With a median follow-up of 20.9 months (range: 11.4–24.6), four patients (66.7%) remained in minimal residual disease (MRD)-negative complete remission (CR), with recurrence-free survival exceeding 24 months. Patients in remission showed increased CD8⁺ and CD4⁺ T cells, total DNTs, and higher frequencies of granzyme-secreting T cells, which were absent in relapsed patients. In vitro, co-culturing AML patient CD8⁺ T cells with allo-DNTs upregulated granzyme B and interferon-γ expression, indicating CD8⁺ T cell activation. These findings suggest that allogeneic DNT immunotherapy is a safe, promising strategy to prevent relapse in high-risk AML patients post-allo-HSCT by combining intrinsic antitumor activity with immune modulation.
ISSN:2162-3619

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