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


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.

SUBMITTER: Gohil SH 

PROVIDER: S-EPMC5543882 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Gohil Satyen Harish SH   Paredes-Moscosso Solange Rosa SR   Harrasser Micaela M   Vezzalini Marzia M   Scarpa Aldo A   Morris Emma E   Davidoff Andrew M AM   Sorio Claudio C   Nathwani Amit Chunilal AC   Della Peruta Marco M  

Oncoimmunology 20170517 7


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 <i>in vitro</i> at exceedingly low concentrations (0.1 ng/mL) and low effector to target rati  ...[more]

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