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An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors

Gohil, SH; Paredes-Moscosso, SR; Harrasser, M; Vezzalini, M; Scarpa, A; Morris, E; Davidoff, AM; ... Della Peruta, M; + view all (2017) An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors. OncoImmunology , 6 (7) , Article e1326437. 10.1080/2162402X.2017.1326437. Green open access

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Abstract

We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold. To validate its wider therapeutic potential, we next demonstrated significant cytotoxicity against ovarian cancer in an in vitro and in vivo setting and T-cell-mediated killing of a range of histologically distinct solid tumor cell lines. Overall, our ROR1 BiTE represents a promising immunotherapy approach, because of its ability to target a broad range of malignancies, many with significant unmet therapeutic needs.

Type: Article
Title: An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/2162402X.2017.1326437
Publisher version: http://dx.doi.org/10.1080/2162402X.2017.1326437
Language: English
Additional information: © Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M. Davidoff, Claudio Sorio, Amit Chunilal Nathwani, and Marco Della Peruta. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
Keywords: Science & Technology, Life Sciences & Biomedicine, Oncology, Immunology, Cancer, Immunotherapy, ROR1, Chronic Lymphocytic-Leukemia, Receptor Tyrosine Kinase, Stem-Cells, In-Vitro, Antibody, Cancer, Expression, Therapy, Blinatumomab, Safety
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 Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/1571715
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