Safety and Efficacy of Ex Vivo Expanded Healthy Donor-Derived Double Negative T Cells for the Treatment of AML Relapsed after Allogeneic Stem Cell Transplantation: A First in-Human Phase I/IIa Clinical Trial

作者：Baolin Tang, Jongbok Lee, Siqi Cheng, Wen Yao, Dongyao Wang, Mei‐Juan Tu, Zhiqiang Xiang, Liangquan Geng, Mingxia Wang, Ping Qiang, Pingping Teng, Guangyu Sun, Tianzhong Pan, Huilan Liu, Liming Yang, Zimin Sun, Li Zhang, Xiaoyu Zhu · 发表于：Blood · 年份：2020 · DOI：10.1182/blood-2020-141505 · 被引用次数：15 · 研究领域：CAR-T cell therapy research、Hematopoietic Stem Cell Transplantation、Acute Myeloid Leukemia Research

BACKGROUND Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the main cause of treatment failure for patients with acute myeloid leukemia (AML). Conventional treatments such as donor lymphocyte infusions (DLI) or secondary allo-HSCT as a monotherapy or in combination with novel agents or immunotherapy showed limited improvements on long-term survival. Our previous studies have shown that a rare subset of CD4- and CD8- double negative T cells (DNTs) expanded from periphery of healthy donors are effective in targeting AML cells in vitro and in xenograft models. Also, allogeneic DNTs can be used as an off-the-shelf adoptive cellular therapy (ACT) for AML. We undertook a first in-human phase I/IIa trial to assess the safety and efficacy of escalating doses of DNTs for the treatment of AML patients relapsed post allo-HSCT. This study protocol was approved by Chinese Ethics Committee of Registering Clinical Trials. Informed consent was obtained in accordance with the Declaration of Helsinki. The trial was registered on the Chinese Clinical Trial Registry (ChiCTR-IPR-1900022795). METHODS From June 2019 to June 2020, 12 patients with relapsed AML after allo-HSCT were enrolled in the trials. Three patients received HLA-matched sibling stem cell transplant, and 9 patients received umbilical cord blood transplantation (UCBT). Hematological relapse was found in 9 cases, and molecular relapsed in 3 cases. None of the patients were able to obtain DLI from...