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Mol Ther. 2015 Aug;23(8):1358-1367. doi: 10.1038/mt.2015.102. Epub 2015 Jun 8.

HIV-specific Immunity Derived From Chimeric Antigen Receptor-engineered Stem Cells.

Author information

1
Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
2
Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
3
UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
4
Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. Electronic address: skitchen@ucla.edu.

Abstract

The human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte (CTL) response is critical in controlling HIV infection. Since the immune response does not eliminate HIV, it would be beneficial to develop ways to enhance the HIV-specific CTL response to allow long-term viral suppression or clearance. Here, we report the use of a protective chimeric antigen receptor (CAR) in a hematopoietic stem/progenitor cell (HSPC)-based approach to engineer HIV immunity. We determined that CAR-modified HSPCs differentiate into functional T cells as well as natural killer (NK) cells in vivo in humanized mice and these cells are resistant to HIV infection and suppress HIV replication. These results strongly suggest that stem cell-based gene therapy with a CAR may be feasible and effective in treating chronic HIV infection and other morbidities.

PMID:
26050990
PMCID:
PMC4817874
DOI:
10.1038/mt.2015.102
[Indexed for MEDLINE]
Free PMC Article

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