TCR transfer into human T cells with ecotropic vectors

Mainz, April 23, 2014 – Efficient retroviral transduction of T cells is crucial for adoptive T-cell transfer in cancer immunotherapy. As now published in the April issue of Gene Therapy, TRON researchers have successfully used transient expression of a receptor protein to make human T cells susceptible for otherwise murine specific retroviruses.

Current state of the art techniques to transduce human T cells rely on the use of amphotropic retroviruses, which imply several drawbacks related to their potential risks. In this study, synthetic mRNA was utilized to encode the receptor protein for murine specific retroviruses. By expression of this protein, the cells became transduceable to ecotropic vectors, adding one further line of safety to the generation of adoptive T-cells.

The resulting ecotropic transductions were more efficient than standard amphotropic techniques performed in parallel, and furthermore preferentially targeted naïve T cells. Moreover, the demonstrated ecotropic TCR transductions resulted in enhanced antigen-specific restimulation of primary T cells.

The study by TRON doctoral candidate Lars Koste et al. enables synthetic mRNA mediated ecotropic transductions as a versatile, safe and potent tool to prepare human T cells for adoptive transfer and immunotherapy. This may contribute to making ecotropic vectors for clinical adoptive T-cell transfer a reachable goal.

http://www.ncbi.nlm.nih.gov/pubmed/?term=24694535
http://www.nature.com/gt/journal/vaop/ncurrent/full/gt201425a.html