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Updated: Mar 29, 2026

Imaging CD19+ B Cells in an Experimental Autoimmune Encephalomyelitis Mouse Model using Positron Emission Tomography
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[Developing anti-CD20 molecules and B cell depletion in multiple sclerosis].

Zsolt Illés1,2,3,4,5

  • 1Department of Neurology, Odense University Hospital, Odense, Dánia.

Ideggyogyaszati Szemle
|March 28, 2026
PubMed
Summary

Anti-CD20 therapies, including monoclonal antibodies, are effective for multiple sclerosis (MS) by depleting B cells. Fc engineering enhances antibody-dependent cellular cytotoxicity (ADCC) for improved efficacy in MS treatment.

Keywords:
B cell depletionFc regionanti-CD20multiple sclerosisublituximab

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Area of Science:

  • Immunology
  • Neurology
  • Pharmacology

Background:

  • Anti-CD20 monoclonal antibodies have been recognized for multiple sclerosis (MS) treatment since 2008.
  • Approved therapies include ocrelizumab, ofatumumab, and ublituximab; rituximab remains off-label.
  • B cell depletion occurs via complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).

Purpose of the Study:

  • To review the structure and mechanisms of action of anti-CD20 antibodies.
  • To outline advancements in antibody humanization and Fc engineering for enhanced efficacy and tolerability.
  • To present clinical data on ublituximab and discuss strategies for effective B cell depletion in MS.

Main Methods:

  • Review of existing literature on anti-CD20 antibody mechanisms and clinical data.
  • Analysis of Fc engineering techniques to improve antibody-dependent cellular cytotoxicity (ADCC).
  • Examination of factors modulating ADCC, including Fc glycosylation and FcγRIIIa polymorphisms.

Main Results:

  • The relative contribution of CDC and ADCC varies among anti-CD20 antibodies.
  • NK cell-mediated ADCC is influenced by antibody glycosylation and FcγRIIIa genetic variations.
  • Fc engineering can enhance ADCC and mitigate the impact of FcγRIIIa polymorphisms.

Conclusions:

  • Anti-CD20 antibodies offer effective B cell depletion for MS treatment.
  • Fc engineering represents a promising strategy to optimize anti-CD20 antibody efficacy and tolerability.
  • Further strategies for B cell depletion are crucial for managing MS.