Substantial progress has been made over the past decades and has led to improved engineering technologies, safety and efficacy of the first generation of therapeutic Abs in neurology. These developments, along with a greater understanding of the immunomodulatory properties of Abs, have paved the way for the next generation of new and improved Ab-based treatment platforms. Fc-engineering technologies are now being used to specifically address and improve particular effector functions and safety issues to create entirely new Ab-based therapies for immune-mediated neurological diseases. Effector functions of therapeutic Abs can further be improved by regulating FcγR binding and signalling. It remains to be demonstrated, however, that enhanced effector functions indeed translate into higher clinical efficacy. Improving access to the CNS is another important target for Ab- and Ig-domain-based therapies. With dedicated attention to basic, translational and clinical research, we shall soon build even better, more effective and safe Ab-based treatment platforms able to target CNS diseases currently not amenable to immunotherapy.
ADAs = antidrug-antibodies; Abdegs = antibodies that enhance IgG degradation; ADCC = antibody-dependent cell-mediated cytotoxicity; Fc = crystallizable fragment; IR = insulin receptor; ITP = immune thrombocytopenia; FcγR = Fc receptor; FcRn = neonatal Fc receptor; IVIg = intravenous immunoglobulins; (m)Abs = (monoclonal) antibodies; NMOSD = neuromyelitis optica spectrum disorder
This work has been supported by grants to T.R. from Else-Kröner Fresenius Foundation (2018_A03), German Research Foundation (RU 2169/2-1) and Bundesministerium für Bildung und Forschung (BMBF) (01EC1901A). F.N. was supported by the Deutsche Forschungsgemeinschaft (DFG) project grants DFG-TRR130-P13 and D-A-CH NI 711/9-1 to F.N. F.N. was further supported by National Institute of Allergy and Infectious Diseases (NIAID) grant U01 AI-148119-01. H.W.'s research is funded by the Bundesministerium für Bildung und Forschung (BMBF), German Research Foundation, Else-Kröner Fresenius Foundation, Hertie Foundation, Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen, Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Münster and Sanofi-Genzyme. Research in J.D.L.'s laboratory is supported by the Swiss National Science Foundation (31003A_169664) and the German Research Foundation (SFB-CRC128; LU 900/3-1).
Brain. 2022;145(4):1229-1241. © 2022 Oxford University Press