Fc-engineering significantly improves the recruitment of immune effector cells by anti-ICAM-1 antibody MSH-TP15 for myeloma therapy.

Despite several therapeutic advances, patients with multiple myeloma (MM) require additional treatment options since no curative therapy exists yet. In search of a novel therapeutic antibody, we previously applied phage display with myeloma cell screening and developed TP15, a scFv targeting intercellular adhesion molecule 1 (ICAM-1/CD54). To more precisely evaluate the antibody's modes of action, fully human IgG1 antibody variants were generated bearing wild-type (MSH-TP15) or mutated Fc to either enhance (MSH-TP15 Fc-eng.

A novel Fc-engineered human ICAM-1/CD54 antibody with potent anti-myeloma activity developed by cellular panning of phage display libraries.

To identify antibodies suitable for multiple myeloma (MM) immunotherapy, a cellular screening approach was developed using plasma cell lines JK-6L and INA-6 and human synthetic single-chain fragment variable (scFv) phage libraries. Isolated phage antibodies were screened for myeloma cell surface reactivity. Due to its binding characteristics, phage PIII-15 was selected to generate the scFv-Fc fusion protein TP15-Fc with an Fc domain optimized for FcγRIIIa binding.