Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis

Tacke S, Chunder R, Schropp V, Urich E, Kürten S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 23

Article Number: 3172

Journal Issue: 6

DOI: 10.3390/ijms23063172

Abstract

Successful therapy with anti-CD20 monoclonal antibodies (mAbs) has reinforced the key role of B cells in the immunopathology of multiple sclerosis (MS). This study aimed to determine the effects of a novel class of anti-CD20 mAbs on vascular and extravascular central nervous system (CNS)-infiltrating B cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male hCD20xhIgR3 mice and wild-type C57BL/6 (B6) mice were immunized with human myelin oligodendrocyte glycoprotein (MOG)1–125 to induce EAE. While hCD20xhIgR3 mice were injected intravenously with an anti-human CD20 mAb (5 mg/kg) (rituximab (a type I anti-CD20 mAb) or obinutuzumab (a type II anti-CD20 mAb), B6 mice received the anti-mouse CD20 antibody 18B12. Neither mAb affected clinical disease or serum antibody levels. Obinutuzumab and rituxi-mab had an impact on splenic and CNS-infiltrated B cells with slightly differential depletion effi-cacy. Additionally, obinutuzumab had beneficial effects on spinal cord myelination. B cell depletion rates in the 18B12/B6 model were comparable with those observed in obinutuzumab-treated hCD20xhIgR3 mice. Our results demonstrate the usefulness of anti-CD20 mAbs for the modulation of B cell-driven peripheral immune response and CNS pathology, with type II antibodies potentially being superior to type I in the depletion of tissue-infiltrating B cells.

Authors with CRIS profile

Involved external institutions

F. Hoffmann-La Roche Ltd Switzerland (CH)

How to cite

APA:

Tacke, S., Chunder, R., Schropp, V., Urich, E., & Kürten, S. (2022). Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis. International Journal of Molecular Sciences, 23(6). https://dx.doi.org/10.3390/ijms23063172

MLA:

Tacke, Sabine, et al. "Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis." International Journal of Molecular Sciences 23.6 (2022).

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