Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia. Academic Article uri icon

Overview

abstract

  • Acute myeloid leukemia (AML) is a disease with high incidence of relapse that is originated and maintained from leukemia stem cells (LSCs). Hematopoietic stem cells can be distinguished from LSCs by an array of cell surface antigens such as CD123, thus a candidate to eliminate LSCs using a variety of approaches, including CAR T cells. Here, we evaluate the potential of allogeneic gene-edited CAR T cells targeting CD123 to eliminate LSCs (UCART123). UCART123 cells are TCRαβneg T cells generated from healthy donors using TALEN® gene-editing technology, decreasing the likelihood of graft vs host disease. As safety feature, cells express RQR8 to allow elimination with Rituximab. UCART123 effectively eliminates AML cells in vitro and in vivo with significant benefits in overall survival of AML-patient derived xenograft mice. Furthermore, UCART123 preferentially target AML over normal cells with modest toxicity to normal hematopoietic stem/progenitor cells. Together these results suggest that UCART123 represents an off-the shelf therapeutic approach for AML.

publication date

  • April 28, 2022

Research

keywords

  • Hematopoietic Stem Cell Transplantation
  • Leukemia, Myeloid, Acute

Identity

PubMed Central ID

  • PMC9050731

Scopus Document Identifier

  • 85128905059

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.10.073

PubMed ID

  • 35484102

Additional Document Info

volume

  • 13

issue

  • 1