e15621 Background: The treatment of metastatic testis cancer is by far the gold standard for treating metastatic solid cancers: over 90% of men diagnosis with metastatic testis cancer are completely cured with current therapies. What seems to be lost and somewhat surprising within this truly remarkable therapeutic cancer success in treating a metastatic cancer is the fact that in United States alone there are still over 400 young men who died from this disease because they do not respond to current therapies. Thus, despite the tremendous clinical success with treating this disease, there is still a strong unmet need to develop new treatments for men with metastatic testis cancer who fall outside the celebration of this disease as being completely cured. Methods: The human germ cell tumor embryonal carcinoma line, TERA-1. was used to generate purified testis cancer-specific cell membrane antigens to immunize mice and generated antibodies, by standard conventional mouse B cell hybridoma protocols. Isolated monoclonal antibodies where tested by ELISA and SDS-PAGE Western blotting to identify testis cancer specific antibodies. Testis cancer positive antibodies were further screen in an antibody-drug-conjugate screen to determine if the monoclonal antibody could function as a antibody-drug-conjugate therapeutic drug for metastatic testis cancer. Results: Dozens of monoclonal antibodies were generated with our antibody screen. Based on the screen results, a lead monoclonal antibody, named Bstrongomab, was selected for further development as a testis cancer therapeutic antibody. Bstrongomab is an IgG1 monoclonal antibody specific to the human embryonic cell marker, and testis cancer marker, TRA-1-60, a carbohydrate molecule which has been identified over 4 decades ago as a true human testis cancer marker. A human/mouse chimeric version of Bstrongomab was created - Bstrongximab - as a human therapeutic antibody. An antibody-drug-conjugate using Bstrongximab and the toxic payload MMAE (Monomethyl auristatin E) was developed and tested in pre-clinical human cancer testis in-vitro and in-vivo models and showed to be a powerful testis cancer therapeutic drug targeting TRA-1-60. Conclusions: Bstrongximab-MMAE is a novel therapeutic antibody-drug-conjugate which targets the testis cancer antigen TRA-1-60. TRA-1-60 is not expressed in normal tissues. Bstrongximab-MMAE is a new cancer drug ready to move into clinical trials for men with metastatic cancer that do not respond with current therapy protocols.
Affinity profiling of monoclonal antibody and antibody-drug-conjugate preparations by coupled liquid chromatography-surface plasmon resonance biosensing