Novel FGFR4 binders and CARs
Novel binders targeting the membrane proximal domain of FGFR4 and CARs and CAR T cells incorporating the binder
Background
Overexpression of fibroblast growth factor receptor 4 (FGFR4) is seen in many types of solid tumors including cancers of the breast, liver, colon, prostate and in the pediatric solid tumor rhabdomyosarcoma. FGFR4 targeted therapeutics including small molecule inhibitors, antibodies and CAR T cells are currently in development
Technology
We have developed novel chimeric antigen receptors (CARs) that specifically target the plasma membrane proximal extracellular domain of FGFR4. These include CARs containing Fab binders, in addition to CARs containing single chain domain antibody binders that are entirely of human origin. T cells expressing the FGFR4 CARs successfully targeted and lysed RH30 cell lines in vitro and expressed interferon γ.
Unlike previous therapies that focus on distal domains, this proximal targeting optimizes the immunological synapse distance, significantly enhancing CAR-T cell potency and cytotoxicity. These CARs are novel compositions of matter that can be incorporated into other therapeutic immune effector cells.
Benefits
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Novel FGFR4 specific binders and CARs
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Membrane proximal domain targeting of FGFR4
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CARs contain single chain domain antibody binders with entirely human sequence
Applications
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Antibody based therapy for FGFR4 expressing cancers
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CAR T cell therapy for FGFR4 expressing cancers
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Pediatric soft tissue sarcoma therapy
Additional info
US Patent Allowed