An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors
| Autor: | Gohil, S, Paredes-Moscosso, S, Harrasser, M, Vezzalini, M, Scarpa, A, Morris, E, Davidoff, A, Sorio, C, Nathwani, A, Della Peruta, M |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Oncoimmunology OncoImmunology, Vol 6, Iss 7 (2017) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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