1. T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
- Author
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Alessia Nottebrock, Eric Tartour, Klaus-Peter Janssen, Nicholas Tokarew, Christine Hoerth, Moritz Thomas, Johannes Lutz, Niels Halama, Martin Jastroch, Öykü Umut, Simon Grassmann, Andrew S. Liss, Maximilian Reichert, Stefanie Lesch, Philipp Metzger, S Stoiber, Benjamin Larimer, Justyna Ogonek, Bruno L. Cadilha, M. Kurzay, Jasper N. Pruessmann, Felicitas Rataj, Mauro Di Pilato, Max Schnurr, Viktoria Blumenberg, Stephan Kruger, Sebastian Kobold, Matthias Seifert, Lene Vimeux, Zahra Dantes, Carsten Marr, Klara Dorman, M. Benmebarek, C. Karches, Moritz Rapp, Duc Huynh, Stefan Endres, Lars M. König, Thi Anh-Dao Tran, Constanze Heise, Dario Dhoqina, Daniel Lamp, Marion Subklewe, Thorsten R. Mempel, Emmanuel Donnadieu, Ruth Grünmeier, Anna Reischer, Svenja Ruehland, Michael Hristov, Adrian Gottschlich, Taisuke Baba, Peter Duewell, Steffen Ormanns, Sandy Joaquina, Simon Rothenfusser, Thomas Hank, Arman Oener, Remco T. A. Megens, Biomedische Technologie, and RS: Carim - B01 Blood proteins & engineering
- Subjects
0301 basic medicine ,RECRUITMENT ,EXPRESSION ,INFILTRATING LYMPHOCYTES ,medicine.medical_treatment ,T-Lymphocytes ,Cell- and Tissue-Based Therapy ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,CXC CHEMOKINE ,Immunotherapy, Adoptive ,TRANSDUCTION ,Article ,Cell therapy ,Mice ,03 medical and health sciences ,Chemokine receptor ,0302 clinical medicine ,Immune system ,Cancer immunotherapy ,Antigen ,Pancreatic cancer ,medicine ,Animals ,Humans ,IMMUNOTHERAPY ,Receptors, CXCR6 ,Chemistry ,LOCALIZATION ,medicine.disease ,CHIMERIC ANTIGEN RECEPTOR ,CANCER ,C-X-C Chemokine Receptor Type 6 ,Chimeric antigen receptor ,Computer Science Applications ,Pancreatic Neoplasms ,030104 developmental biology ,IMMUNE CELLS ,Mesothelin ,Cancer research ,Receptors, Chemokine ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer.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.
- Published
- 2021
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