Logo Logo
Switch Language to German

Klausz, Katja; Cieker, Michael; Kellner, Christian; Roesner, Thies; Otte, Anna; Krohn, Steffen; Lux, Anja; Nimmerjahn, Falk; Valerius, Thomas; Gramatzki, Martin and Peipp, Matthias (2021): Fc-engineering significantly improves the recruitment of immune effector cells by anti-ICAM-1 antibody MSH-TP15 for myeloma therapy. In: Haematologica, Vol. 106, No. 7: pp. 1857-1866

Full text not available from 'Open Access LMU'.


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 single-chain fragment variable targeting intercellular adhesion molecule 1 (ICAM-1/CD54). In order to more precisely evaluate the antibody's modes of action, fully human immunoglobulin G1 antibody variants were generated bearing the wild-type (MSH-TP15) or mutated fragment crystallizable (Fc-engineered [Fc-eng.]) region to either enhance (MSH-TP15 Fc-eng.) or prevent (MSH-TP15 Fc knockout [Fc k.o.]) Fc gamma receptor binding. Especially MSH-TP15 Fc-eng. induced significant antibody-dependent cell-mediated cytotoxicity against malignant plasma cells by recruiting natural killer cells and engaged macrophages for antibody-dependent cellular phagocytosis of tumor cells. Binding studies with truncated ICAM-1 demonstrated MSH-TP15 binding to ICAM-1 domain 1-2. Importantly, MSH-TP15 and MSH-TP15 Fc-eng. both prevented myeloma cell engraftment and significantly prolonged survival of mice in an intraperitoneal xenograft model. In the subcutaneous model MSH-TP15 Fc-eng. was superior to MSH-TP15, whereas MSH-TP15 Fc k.o. was not effective in either of the models - reflecting the importance of Fc-dependent mechanisms of action also in vivo. The efficient recruitment of immune cells and the observed anti-tumor activity of the Fc-engineered MSH-TP15 antibody hold significant potential for myeloma immunotherapy.

Actions (login required)

View Item View Item