In:
Life Science Alliance, Life Science Alliance, LLC, Vol. 2, No. 2 ( 2019-04), p. e201900367-
Abstract:
Adoptive transfer of TCR transgenic T cells holds great promise for treating various cancers. So far, mainly semi-randomly integrating vectors have been used to genetically modify T cells. These carry the risk of insertional mutagenesis, and the sole addition of an exogenous TCR potentially results in the mispairing of TCR chains with endogenous ones. Established approaches using nonviral vectors, such as transposons, already reduce the risk of insertional mutagenesis but have not accomplished site-specific integration. Here, we used CRISPR-Cas9 RNPs and adeno-associated virus 6 for gene targeting to deliver an engineered TCR gene specifically to the TCR alpha constant locus, thus placing it under endogenous transcriptional control. Our data demonstrate that this approach replaces the endogenous TCR, functionally redirects the edited T cells’ specificity in vitro , and facilitates potent tumor rejection in an in vivo xenograft model .
Type of Medium:
Online Resource
ISSN:
2575-1077
DOI:
10.26508/lsa.201900367
Language:
English
Publisher:
Life Science Alliance, LLC
Publication Date:
2019
detail.hit.zdb_id:
2948687-7
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