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Lesch, S.* ; Blumenberg, V.* ; Stoiber, S.* ; Gottschlich, A.* ; Ogonek, J.* ; Cadilha, B.L.* ; Dantes, Z.* ; Rataj, F.* ; Dorman, K.* ; Lutz, J.* ; Karches, C.H.* ; Heise, C.* ; Kurzay, M.* ; Larimer, B.M.* ; Grassmann, S.* ; Rapp, M.* ; Nottebrock, A.* ; Krüger, S.* ; Tokarew, N.* ; Metzger, P.* ; Hoerth, C.* ; Benmebarek, M.R.* ; Dhoqina, D.* ; Grünmeier, R.* ; Seifert, M.* ; Oener, A.* ; Umut, Ö.* ; Joaquina, S.* ; Vimeux, L.* ; Tran, T.* ; Hank, T.* ; Baba, T.* ; Huynh, D.* ; Megens, R.T.A.* ; Janssen, K.P.* ; Jastroch, M. ; Lamp, D. ; Ruehland, S.* ; Di Pilato, M.* ; Pruessmann, J.N.* ; Thomas, M. ; Marr, C. ; Ormanns, S.* ; Reischer, A.* ; Hristov, M.* ; Tartour, E.* ; Donnadieu, E.* ; Rothenfußer, S. ; Duewell, P.* ; König, L.M.* ; Schnurr, M.* ; Subklewe, M.* ; Liss, A.S.* ; Halama, N.* ; Reichert, M.* ; Mempel, T.R.* ; Endres, S. ; Kobold, S.

T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours.

Nat. Bio. Eng., DOI: 10.1038/s41551-021-00737-6 (2021)
DOI Order publishers version
Open Access Green: Postprint online available 01/2022
The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that forced expression of C-X-C chemokine receptor type 6 (whose ligand is highly expressed by human and murine pancreatic cancer cells and tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained anti-tumoral activity and prolonged animal survival only when co-expressing C-X-C chemokine receptor type 6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Chimeric Antigen Receptor; Cxc Chemokine; Infiltrating Lymphocytes; Immune Cells; Immunotherapy; Cancer; Recruitment; Expression; Localization; Transduction
ISSN (print) / ISBN 2157-846X
e-ISSN 2157-846X
Publisher Nature Publishing Group
Publishing Place London ; New York NY ; Tokyo
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)
Institute of Diabetes and Obesity (IDO)
Institute of Computational Biology (ICB)
Grants Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)