dc.contributor.author | Raj, D | en_US |
dc.contributor.author | Yang, M-H | en_US |
dc.contributor.author | Rodgers, D | en_US |
dc.contributor.author | Hampton, EN | en_US |
dc.contributor.author | Begum, J | en_US |
dc.contributor.author | Mustafa, A | en_US |
dc.contributor.author | Lorizio, D | en_US |
dc.contributor.author | Garces, I | en_US |
dc.contributor.author | Propper, D | en_US |
dc.contributor.author | Kench, JG | en_US |
dc.contributor.author | Young, TS | en_US |
dc.contributor.author | Aicher, A | en_US |
dc.contributor.author | Heeschen, C | en_US |
dc.date.accessioned | 2018-09-04T08:50:36Z | |
dc.date.available | 2018-07-13 | en_US |
dc.date.issued | 2018-08-18 | en_US |
dc.date.submitted | 2018-08-30T11:06:51.856Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/44123 | |
dc.description.abstract | OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a disease of unmet medical need. While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects. Switchable CAR-T cells whereby activity of the CAR-T cell is controlled by dosage of a tumour antigen-specific recombinant Fab-based 'switch' to afford a fully tunable response may overcome this translational barrier. DESIGN: In this present study, we have used conventional and switchable CAR-T cells to target the antigen HER2, which is upregulated on tumour cells, but also present at low levels on normal human tissue. We used patient-derived xenograft models derived from patients with stage IV PDAC that mimic the most aggressive features of PDAC, including severe liver and lung metastases. RESULTS: Switchable CAR-T cells followed by administration of the switch directed against human epidermal growth factor receptor 2 (HER2)-induced complete remission in difficult-to-treat, patient-derived advanced pancreatic tumour models. Switchable HER2 CAR-T cells were as effective as conventional HER2 CAR-T cells in vivo testing a range of different CAR-T cell doses. CONCLUSION: These results suggest that a switchable CAR-T system is efficacious against aggressive and disseminated tumours derived from patients with advanced PDAC while affording the potential safety of a control switch. | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Gut | en_US |
dc.rights | This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/. | |
dc.subject | immunotherapy | en_US |
dc.subject | liver metastases | en_US |
dc.subject | pancreatic cancer | en_US |
dc.subject | stem cells | en_US |
dc.title | Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma. | en_US |
dc.type | Article | |
dc.rights.holder | © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ. | |
dc.identifier.doi | 10.1136/gutjnl-2018-316595 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30121627 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2018-07-13 | en_US |