Lowering mTORC1 Drives CAR T-Cells Home in Acute Myeloid Leukemia

Clin Cancer Res. 2021 Nov 1;27(21):5739-5741. doi: 10.1158/1078-0432.CCR-21-2574. Epub 2021 Sep 1.

Abstract

Cellular therapies have demonstrated limited efficacy thus far in acute myeloid leukemia (AML). A recent study shows that mTOR complex 1 activation downregulated CXCR4 reducing marrow infiltration of EpCAM-targeting chimeric antigen receptor (CAR) T-cells in AML. Abrogating mTOR signaling by cotreatment with mTOR inhibitors during IL2-mediated ex vivo expansion upregulated CXCR4 and bolstered bone marrow migration and AML elimination by CAR T-cells.See related article by Nian et al., p. 6026.

Publication types

  • Research Support, N.I.H., Extramural
  • Comment

MeSH terms

  • Humans
  • Immunotherapy, Adoptive
  • Leukemia, Myeloid, Acute* / therapy
  • MTOR Inhibitors
  • Mechanistic Target of Rapamycin Complex 1
  • Receptors, Chimeric Antigen* / genetics
  • T-Lymphocytes

Substances

  • MTOR Inhibitors
  • Receptors, Chimeric Antigen
  • Mechanistic Target of Rapamycin Complex 1