Several high-affinity monoclonal antibodies can be used to treat FGFR4-related diseases such as rhabdomyosarcoma and cancers of the liver, lung, pancreas, ovary and prostate. In particular, these antibodies have been used to generate ADCs and CARs specifically targeting and killing cancer cells.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Although current treatments for primary disease are relatively successful, metastatic RMS is generally accompanied by a dismal prognosis. Thus, there is a public health need for the development of new therapies for metastatic RMS.
Fibroblast Growth Factor Receptor 4 (FGFR4) is a cell surface protein that is highly expressed in RMS as well as in liver, lung, pancreatic, ovarian, and prostate cancers. Researchers in NCI's Genetics Branch found that high FGFR4 expression in RMS patients is often associated with advanced disease, rapid disease progression, and poor survival. The correlation between FGFR4 expression and highly aggressive RMS makes the protein an attractive target for treatment. Specific targeting of FGFR4 specifically may attack cancer cells while leaving healthy, essential cells unaffected.
- Development of unconjugated antibody therapeutics
- Development of antibody-drug conjugates (ADCs) and recombinant immunotoxins
- Development of chimeric antigen receptors (CARs) and T cell receptors
- Development of bispecific antibody therapeutics
- Development of diagnostic agents for detecting FGFR4-positive cancers
- High affinity and specificity of the antibodies allows more selective targeting of cancer cells, reducing the potential for side effects during therapy
- Multiple antibodies available
- Potential to address significant unmet medical need
Javed Khan MD (NCI), Sivasubramanian Baskar (NCI), Rimas J Orentas (NCI), Dimiter S Dimitrov (NCI), Zhongyu Zhu (NCI)
- U.S. Patent Filed: U.S. Patent Application Number PCT/US2016/052496 , Filed 19 Sep 2016
- U.S. Provisional: U.S. Provisional Patent Application Number 62/221,045 , Filed 20 Sep 2015