异基因双阴性 T 细胞预防性输注作为免疫调节剂预防高危 AML 患者 Allo-HSCT 后复发：一项 I 期试验

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.