Anti-myeloma activity of the novel ADCC-optimized human CD54 (ICAM-1) antibody MSH-TP15e.

e14009Background: Monoclonal antibodies directed against different target antigens have proven efficacy in cancer therapy. Recently, daratumumab and elotuzumab became the first antibodies approved for the treatment of multiple myeloma (MM). Due to the substantial number of patients still in need for long-term disease control, the investigation of additional target structures and potent molecule formats for antibody-based therapy of MM remains important. Methods: Human synthetic phage display libraries were screened with a cellular screening strategy and one clone was selected based on its favorable binding characteristics to various MM cell lines and patient-derived CD138-positive malignant plasma cells. CD54/ICAM-1 was identified as target antigen. Fully human IgG1 antibody variants with mutations in the Fc domain enhancing selected effector functions were generated and analyzed for their capacity to kill MM cells in vitro and in the INA-6 myeloma xenograft model. Results: MSH-TP15 did not directly induc...