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

Lesch, Stefanie; Blumenberg, Viktoria; Stoiber, Stefan; Gottschlich, Adrian; Ogonek, Justyna; Cadilha, Bruno L; Dantes, Zahra; Rataj, Felicitas; Dorman, Klara; Lutz, Johannes; Karches, Clara H; Heise, Constanze; Kurzay, Mathias; Larimer, Benjamin M; Grassmann, Simon; Rapp, Moritz; Nottebrock, Alessia; Kruger, Stephan; Tokarew, Nicholas; Metzger, Philipp; Hoerth, Christine; Benmebarek, Mohamed-Reda; Dhoqina, Dario; Grünmeier, Ruth; Seifert, Matthias; Oener, Arman; Umut, Öykü; Joaquina, Sandy; Vimeux, Lene; Tran, Thi; Hank, Thomas; Baba, Taisuke; Huynh, Duc; Megens, Remco T A; Janssen, Klaus-Peter; Jastroch, Martin; Lamp, Daniel; Ruehland, Svenja; Di Pilato, Mauro; Pruessmann, Jasper N; Thomas, Moritz; Marr, Carsten; Ormanns, Steffen; Reischer, Anna; Hristov, Michael; Tartour, Eric; Donnadieu, Emmanuel; Rothenfusser, Simon; Duewell, Peter; König, Lars M; Schnurr, Max; Subklewe, Marion; Liss, Andrew S; Halama, Niels; Reichert, Maximilian; Mempel, Thorsten R; Endres, Stefan; Kobold, Sebastian     «

Lesch, Stefanie; Blumenberg, Viktoria; Stoiber, Stefan; Gottschlich, Adrian; Ogonek, Justyna; Cadilha, Bruno L; Dantes, Zahra; Rataj, Felicitas; Dorman, Klara; Lutz, Johannes; Karches, Clara H; Heise, Constanze; Kurzay, Mathias; Larimer, Benjamin M; Grassmann, Simon; Rapp, Moritz; Nottebrock, Alessia; Kruger, Stephan; Tokarew, Nicholas; Metzger, Philipp; Hoerth, Christine; Benmebarek, Mohamed-Reda; Dhoqina, Dario; Grünmeier, Ruth; Seifert, Matthias; Oener, Arman; Umut, Öykü; Joaquina, Sandy; Vim...     »

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.      «

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 subcut...     »