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CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia.
- Source :
-
Journal of hematology & oncology [J Hematol Oncol] 2018 Jan 10; Vol. 11 (1), pp. 7. Date of Electronic Publication: 2018 Jan 10. - Publication Year :
- 2018
-
Abstract
- Background: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment.<br />Methods: We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ΞΆ signaling domain. We further investigate the function of CLL-1 CAR-T cells.<br />Results: The CLL-1 CAR-T cells specifically lysed CLL-1 <superscript>+</superscript> cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1 <superscript>+</superscript> myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression.<br />Conclusions: CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.
- Subjects :
- Animals
Cell Line, Tumor
Female
Humans
Lectins, C-Type analysis
Leukemia, Myeloid, Acute immunology
Male
Membrane Proteins analysis
Mice, Inbred C57BL
T-Lymphocytes immunology
Immunotherapy, Adoptive methods
Lectins, C-Type immunology
Leukemia, Myeloid, Acute therapy
Membrane Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1756-8722
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of hematology & oncology
- Publication Type :
- Academic Journal
- Accession number :
- 29316944
- Full Text :
- https://doi.org/10.1186/s13045-017-0553-5