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Fibroblast Growth Factor Receptor 4 (FGFR4) Monoclonal Antibodies and Methods of Their Use

Summary
Researchers at the National Cancer Institute (NCI) developed several high-affinity monoclonal antibodies to treat Fibroblast Growth Factor Receptor 4 (FGFR4)-related diseases including rhabdomyosarcoma and cancers of the liver, lung, pancreas, ovary and prostate. These antibodies have been used to generate antibody-drug conjugates (ADCs) and chimeric antigen receptors (CARs), which are capable of specifically targeting and killing diseased cells. NCI seeks co-development opportunities or licensees for this technology.
NIH Reference Number
E-264-2015
Product Type
Keywords
  • Monoclonal Antibodies, Fibroblast Growth Factor Receptor 4, FGFR4, Rhabdomyosarcoma, RMS, Immunotherapy, Khan
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

Several Fibroblast Growth Factor Receptor 4 (FGFR4) specific antibodies with binding affinity at the nanomolar range have been successfully developed at the Genetics Branch. These antibodies have been made into different formats of therapeutic including Antibody Drug Conjugate (ADC), Bispecific T cell engager (BiTE) ae well as Chimeric Antigen Receptor (CAR)-T cells.

Proof of principle experiments have shown that when treated with FGFR4 positive tumor cells:  

  1. FGFR4 specific antibodies were able to deliver cytotoxic agents and killed those cells.  
  2. CD3 FGFR4 BiTE were able to recruit T cells to kill those cells. 
  3. FGFR4 CAR-T cell was activated by cancer cells overexpressed FGFR4 and FGFR4 CAR-T cells were able to eliminate target cells both in vitro and in vivo 

These findings are important in Rhabdomyosarcoma (RMS) as researchers at NCI's Genetics Branch found that high FGFR4 is overexpressed in RMS tumors compared with other normal tissue. RMS patients with higher FGFR4 expression 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. 

RMS is a rare, yet 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, these FGFR4 antibody- based therapeutics may fulfill the unmet medical needs for this disease.  Moreover, over expression of FGFR4 has also been reported in other common malignancies including liver, lung, pancreas, ovary and prostate cancers. Therefore, FGFR4 specific therapeutics can also be used for treatment of these diseases. 

Potential Commercial Applications
  • 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
Competitive Advantages
  • 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
Inventor(s)

Javed Khan MD (NCI), Sivasubramanian Baskar (NCI), Rimas J Orentas (NCI), Dimiter S Dimitrov (NCI), Zhongyu Zhu (NCI)

Development Stage
Patent Status
  • 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
  • U.S. Patent Filed: U.S. Patent Application Number 15/761,398, Filed 19 Mar 2018
  • Foreign Filed: CA - Patent Application 2996205, Filed 19 Sep 2016
  • Foreign Filed: EP - Patent Application 16778536.9, Filed 19 Sep 2016
Therapeutic Area
Updated
Wednesday, September 16, 2020