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, José L. Ochoa-Bayona, Justin C. Boucher, José A. Guevara-Patiño, David A. Sallman, Jeffrey E. Lancet, Joseph A. Pidala, Kumar Karyampudi, Frederick L. Locke, Claudio Anasetti, Marco L. Davila · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-202363 · 被引用次数：2 · 研究领域：CAR-T cell therapy research、RNA Interference and Gene Delivery、CRISPR and Genetic Engineering

Background Patients with adverse risk acute myeloid leukemia (AML) by European LeukemiaNet (ELN) risk stratification are at high risk (~50%) of relapse after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT). We developed a novel cellular therapy using ex vivo expanded donor-derived gamma delta T (GDT) cells to prevent post-HCT relapse and cure more patients with adverse risk AML. GDT cells that are rare in circulating blood have MHC-independent potent antitumor cytotoxicity against AML. They cause no graft-versus-host-disease (GVHD) in preclinical studies, which allows the potential for a healthy donor-derived cellular immunotherapy for AML. Methods This first-in-human trial enrolled patients with ELN adverse risk AML who received either HLA-identical sibling donor (MSD) or haploidentical donor RIC alloHCT. The same donor used for HCT underwent non-mobilized leukapheresis for large scale expansion of GDT cells with use of artificial antigen presented cells (Boucher J. Immunother. 2023). Expanded GDT cells were infused to patients between days 60-100 after alloHCT in the absence of uncontrolled infection and/or GVHD requiring systemic steroids. The trial followed a 3+3 design to study the primary endpoint of maximum-tolerated dose (MTD) of donor GDT cell infusion. Three dose levels (DL) of GDT cells were studied where DL1 was 6.25 x 106 cells/kg, DL2 was 3.13 x 107 cells/kg and DL3 was 1.10 x 108 cells/kg. Dose-limiting toxicities (D...