期刊
ONCOIMMUNOLOGY
卷 6, 期 7, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1326437
关键词
Cancer; Immunotherapy; ROR1
资金
- National Institute for Health Research Program Grant
- Wellcome Trust Clinical Fellowship
- Associazione Italiana Ricerca sul Cancro [AIRC 12182]
- National Institute for Health Research (NIHR) Blood and Transplant Research Unit (BTRU) in Stem Cells and Immunotherapy at UCL
- NHS Blood and Transplant (NHSBT)
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.
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