CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia

Diogo Gomes-Silva, Erden Atilla, Pinar Ataca Atilla, Feiyan Mo, Haruko Tashiro, Madhuwanti Srinivasan, Premal Lulla, Rayne H. Rouce, Joaquim M.S. Cabral, Carlos A. Ramos, Malcolm Brenner, Maksim Mamonkin

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7 KO ) T cells effectively eliminates CD7 + AML cell lines, primary CD7 + AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7 KO CD7 CAR T cells for the non-myeloablative treatment of CD7 + AML.

Original languageEnglish (US)
Pages (from-to)272-280
Number of pages9
JournalMolecular Therapy
Volume27
Issue number1
DOIs
StatePublished - Jan 2 2019

Keywords

  • CAR T cells
  • CD7
  • acute myeloid leukemia
  • chimeric antigen receptors
  • mouse model

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of 'CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia'. Together they form a unique fingerprint.

Cite this