Phase I Trial of Ex Vivo Expanded Donor Gamma Delta T Cell Immunotherapy to Prevent Acute Myeloid Leukemia Relapse after Allogeneic Transplantation

作者：Nelli Bejanyan, Hany Elmariah, Jongphil Kim, Cheryl A. Cox, Melissa Lowden, Xiaofei Song, Hien Liu, Bin Yu, Kayla Reid, Sean Yoder, Christopher Cubitt, Rawan Faramand, Abu‐Sayeef Mirza, Farhad Khimani, Lia Perez, Jose-Leonel Ochoa-Bayona, Justin C. Boucher, José A. Guevara-Patiño, David A. Sallman, Jeffrey E. Lancet, Joseph Pidala, Kumar Karyampudi, Frederick L. Locke, Claudio Anasetti, Marco L. Davila · 发表于：Transplantation and Cellular Therapy · 年份：2025 · DOI：10.1016/j.jtct.2025.01.015 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、RNA Interference and Gene Delivery、CRISPR and Genetic Engineering

Background Patients with European LeukemiaNet (ELN) adverse risk acute myeloid leukemia (AML) are at high risk (∼40%) of relapse after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT). We used ex vivo expanded donor-derived gamma delta T cells (GDT) cells as a novel cellular therapy to prevent adverse risk AML relapse post-HCT. GDT cells have potent antitumor cytotoxicity against AML and cause no graft-versus-host-disease (GVHD), which allows the potential for a healthy donor-derived cellular immunotherapy for AML. Methods This first-in-human trial enrolled patients with 2022 ELN adverse risk AML in complete remission (CR) who received HLA-identical sibling (MSD) or haploidentical donor RIC alloHCT. The same donor used for HCT underwent leukapheresis for expansion of GDT cells using antigen presented cells. GDT cells were infused to patients between days 60-100 after alloHCT. The trial followed a 3+3 design to study the primary endpoint of maximum-tolerated dose (MTD) of GDT cells. Three GDT cell dose levels (DL) were studied where DL1 was 5 × 10 6 cells/kg (n=3), DL2 was 2.5 × 10 7 cells/kg (n=3) and DL3 was 1 × 10 8 cells/kg (n=6). Dose-limiting toxicities (DLT) were defined as grade 3-4 cytokine release syndrome (CRS), grade 3-4 neurotoxicity, or any grade 4 organ toxicity by CTCAE 5.0. Results Among the 12 treated patients (median age, 63), 7 had pre-HCT detectable measurable residual disease (MRD pos ), and 4 had TP53 mutation/...