T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells

Hillerdal, Victoria (author): Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab

Nilsson, Berith (author): Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab

Carlsson, Björn (author): Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab

Eriksson, Fredrik (author): Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab

Essnd, Magnus (author): Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab

(creator_code:org_t)

2012-09-10
2012
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:39, s. 15877-15881

Related links:: https://www.pnas.org...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

To produce genetically engineered T cells directed against prostate and breast cancer cells, we have cloned the T-cell receptor recognizing the HLA-A2–restricted T-cell recptor γ-chain alternate reading-frame protein (TARP)4–13 epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli. These cells exerted peptide-specific IFN-γ production and cytotoxic activity. Importantly, HLA-A2+ prostate and breast cancer cells expressing TARP were also killed, demonstrating that the TARP4–13 epitope is a physiologically relevant target for T-cell therapy of prostate and breast cancer. In conclusion, we present the cloning of a T cell receptor (TCR) directed against a physiologically relevant HLA-A2 epitope of TARP. To our knowledge this report on engineering of T cells with a TCR directed against an antigen specifically expressed by prostate cells is unique.

By the author/editor: Hillerdal, Victo ...; Nilsson, Berith; Carlsson, Björn; Eriksson, Fredri ...; Essnd, Magnus

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