Identification and validation of anti-TMEFF2-Auristatin E conjugated antibodies in the treatment of prostate cancer.

2557 Background: Current treatments for advanced stage prostate cancer are largely ineffectual, resulting in high mortality and morbidity. Experimental strategies to fulfill this unmet medical need include the use of toxin-based antibody-drug conjugates (ADCs) to specifically target cancer cells in vivo. Using gene expression profiling, TMEFF2 was identified as being selective to prostate cancer and was validated as a target suitable for an ADC approach using pre-clinical xenograft models in vivo. Methods: A panel of antibodies specific to TMEFF2 protein was generated. One antibody was selected on the basis of affinity and in vitro functionality as an ADC to undergo further analysis in vivo. Results: TMEFF2, a gene encoding a plasma membrane protein with 2 follistatin-like domains and one EGF-like domain, was found to exhibit a restricted normal tissue expression profile and was determined to be highly over-expressed in prostate cancer. A monoclonal antibody (mAb) raised against TMEFF2 was used in immunoh...