Targeting of folate receptor β on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells

Rachel C. Lynn, Mathilde Poussin, Anna Kalota, Yang Feng, Philip S. Low, Dimiter S. Dimitrov, Daniel J. Powell

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

T cells expressing a chimeric antigen receptor (CAR) can produce dramatic results in lymphocytic leukemia patients; however, therapeutic strategies for myeloid leukemia remain limited. Folate receptor β (FRβ) is a myeloid-lineage antigen expressed on 70% of acute myeloid leukemia (AML) patient samples. Here, we describe the development and evaluation of the first CARs specific for human FRβ (m909) in vitro and in vivo. m909 CAR T cells exhibited selective activation and lytic function against engineered C30-FRβ as well as endogenous FRβ+ AML cell lines in vitro. In mouse models of human AML, m909 CAR T cells mediated the regression of engrafted FRβ+ THP1 AML in vivo. In addition, we demonstrated that treatment of AML with all-trans retinoic acid (ATRA) enhanced FRβ expression, resulting in improved immune recognition by m909 CAR T cells. Because many cell surface markers are shared between AML blasts and healthy hematopoietic stem and progenitor cells (HSCs), we evaluated FRβ expression and recognition of HSCs by CAR T cells. m909 CAR T cells were not toxic against healthy human CD34+ HSCs in vitro. Our results indicate that FRβ is a promising target for CAR T-cell therapy of AML, whichmay be augmented by combination with ATRA.

Original languageEnglish (US)
Pages (from-to)3466-3476
Number of pages11
JournalBlood
Volume125
Issue number22
DOIs
StatePublished - May 28 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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