Journal
VIRUSES-BASEL
Volume 15, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/v15010202
Keywords
HIV; CAR T cells; CRISPR; Cas9; humanized mice
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This study demonstrates the development of HIV-resistant CAR T cells using CRISPR/Cas9 targeted integration of a CAR cassette into the CCR5 locus. The anti-HIV CAR T cells showed specific lysis of HIV-infected cells in vitro and transiently limited HIV infection in a PBMC humanized mouse model of HIV infection.
Adoptive immunotherapy using chimeric antigen receptor (CAR) T cells has been highly successful in treating B cell malignancies and holds great potential as a curative strategy for HIV infection. Recent advances in the use of anti-HIV broadly neutralizing antibodies (bNAbs) have provided vital information for optimal antigen targeting of CAR T cells. However, CD4+ CAR T cells are susceptible to HIV infection, limiting their therapeutic potential. In the current study, we engineered HIV-resistant CAR T cells using CRISPR/Cas9-mediated integration of a CAR cassette into the CCR5 locus. We used a single chain variable fragment (scFv) of the clinically potent bNAb 10-1074 as the antigen-targeting domain in our anti-HIV CAR T cells. Our anti-HIV CAR T cells showed specific lysis of HIV-infected cells in vitro. In a PBMC humanized mouse model of HIV infection, the anti-HIV CAR T cells expanded and transiently limited HIV infection. In conclusion, this study provides proof-of-concept for developing HIV-resistant CAR T cells using CRISPR/Cas9 targeted integration.
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