We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
T-cell receptor transfer into human T cells with ecotropic retroviral vectors.
- Authors
Koste, L; Beissert, T; Hoff, H; Pretsch, L; Türeci, Ö; Sahin, U
- Abstract
Adoptive T-cell transfer for cancer immunotherapy requires genetic modification of T cells with recombinant T-cell receptors (TCRs). Amphotropic retroviral vectors (RVs) used for TCR transduction for this purpose are considered safe in principle. Despite this, TCR-coding and packaging vectors could theoretically recombine to produce replication competent vectors (RCVs), and transduced T-cell preparations must be proven free of RCV. To eliminate the need for RCV testing, we transduced human T cells with ecotropic RVs so potential RCV would be non-infectious for human cells. We show that transfection of synthetic messenger RNA encoding murine cationic amino-acid transporter 1 (mCAT-1), the receptor for murine retroviruses, enables efficient transient ecotropic transduction of human T cells. mCAT-1-dependent transduction was more efficient than amphotropic transduction performed in parallel, and preferentially targeted naive T cells. Moreover, we demonstrate that ecotropic TCR transduction results in antigen-specific restimulation of primary human T cells. Thus, ecotropic RVs represent a versatile, safe and potent tool to prepare T cells for the adoptive transfer.
- Subjects
CANCER immunotherapy; T cell receptors; RECOMBINANT viruses; CELLULAR signal transduction; GENETIC code; AMINO acid transport; RETROVIRUSES
- Publication
Gene Therapy, 2014, Vol 21, Issue 5, p533
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/gt.2014.25