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Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 7/22/2014, Vol. 111 Issue 29, p10660-10665. 6p. - Publication Year :
- 2014
-
Abstract
- Clinical-grade T cells are genetically modified ex vivo to express chimeric antigen receptors (CARs) to redirect their specificity to target tumor-associated antigens in vivo. We now have developed this molecular strategy to render cytotoxic T cells specific for fungi. We adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ (designated "D-CAR") upon binding with carbohydrate in the cell wall of Aspergillus germ-lings. T cells genetically modified with the Sleeping Beauty system to express D-CAR stably were propagated selectively on artificial activating and propagating cells using an approach similar to that approved by the Food and Drug Administration for manufacturing CD19-specific CAR+ T cells for clinical trials. The D-CAR+ T cells exhibited specificity for β-glucan which led to damage and inhibition of hyphal growth of Aspergillus in vitro and in vivo. Treatment of D-CAR+ T cells with steroids did not compromise antifungal activity significantly. These data support the targeting of carbohydrate antigens by CAFT T cells and provide a clinically appealing strategy to enhance immunity for opportunistic fungal infections using T-cell gene therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 111
- Issue :
- 29
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 97266433
- Full Text :
- https://doi.org/10.1073/pnas.1312789111