Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月2日

查看全文
  • 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

摘要

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.