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Integrin-αvβ6 targeted peptide-toxin therapy in a novel αvβ6-expressing immunocompetent model of pancreatic cancer

Brown, Nicholas F; Murray, Elizabeth R; Cutmore, Lauren C; Howard, Philip; Masterson, Luke; Zammarchi, Francesca; Hartley, John A; ... Marshall, John F; + view all (2024) Integrin-αvβ6 targeted peptide-toxin therapy in a novel αvβ6-expressing immunocompetent model of pancreatic cancer. Pancreatology 10.1016/j.pan.2024.02.013. (In press). Green open access

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Abstract

Previously we reported that a novel αvβ6-specific peptide-drug conjugate (SG3299) could eliminate established human pancreatic ductal adenocarcinoma (PDAC) xenografts. However the development of effective therapies for PDAC, which is an essential need, must show efficacy in relevant immunocompetent animals. Previously we reported that the KPC mouse transgenic PDAC model that closely recapitulates most stages of development of human PDAC, unlike in humans, failed to express αvβ6 on their tumours or metastases. In this study we have taken the KPC-derived PDAC line TB32043 and engineered a variant line (TB32043mb6S2) that expresses mouse integrin αvβ6. We report that orthotopic implantation of the αvβ6 over-expressing TB32043mb6S2 cells promotes shorter overall survival and increase in metastases. Moreover, systemic treatment of mice with established TB32043mb6S2 tumours in the pancreas with SG2399 lived significantly longer (p < 0.001; mean OS 48d) compared with PBS or control SG3511 (mean OS 25.5d and 26d, respectively). Thus SG3299 is confirmed as a promising candidate therapeutic for the therapy of PDAC.

Type: Article
Title: Integrin-αvβ6 targeted peptide-toxin therapy in a novel αvβ6-expressing immunocompetent model of pancreatic cancer
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.pan.2024.02.013
Publisher version: https://doi.org/10.1016/j.pan.2024.02.013
Language: English
Additional information: Copyright © 2024 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10190352
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