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

Journal article

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.

Authors: Gohil, S; Paredes-Moscosso, S; Harrasser, M; Vezzalini, M; Scarpa, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Taylor and Francis
• Journal: OncoImmunology
• Volume: 6
• Issue: 7
• Pages: 1-11
• Publication date: 2017-07-17
• Acceptance date: 2017-04-29
• DOI: 10.1080/2162402x.2017.1326437
• EISSN: 2162-402X
• ISSN: 2162-4011
• Pmid: 28811962
• Language: English
• Keywords: ROR1; Immunotherapy; Cancer