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SM03, an Anti-CD22 Antibody, Converts Cis-to-Trans Ligand Binding of CD22 against α2,6-Linked Sialic Acid Glycans and Immunomodulates Systemic Autoimmune Diseases

Kin L. Wong, Zhengdong Li, Felix Ma, Dong Wang, Nan Song, Chi H. Chong, Ka K. Luk and Shui O. Leung
J Immunol June 10, 2021, ji2100820; DOI: https://doi.org/10.4049/jimmunol.2100820
Kin L. Wong
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Zhengdong Li
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Felix Ma
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Dong Wang
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Nan Song
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Chi H. Chong
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Ka K. Luk
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Shui O. Leung
SinoMab BioScience Ltd., Hong Kong Special Administrative Region, China
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Key Points

  • SM03 (an anti-CD22 mAb) immunomodulates B cells in autoimmunity in a novel mechanism of action.

  • SM03 converts cis-to-trans binding of CD22 to α2,6-linked sialic acid glycans.

  • SM03 induces immunomodulation and immune tolerance of B cells to autoantigens.

Abstract

SM03, an anti-CD22 recombinant IgG1 mAb, is currently in a phase III clinical trial for the treatment of rheumatoid arthritis (NCT04312815). SM03 showed good safety and efficacy in phase I systemic lupus erythematosus and phase II moderate to severe rheumatoid arthritis clinical trials. We propose the success of SM03 as a therapeutic to systemic autoimmune diseases is through the utilization of a novel mechanism of action unique to SM03. CD22, an inhibitory coreceptor of the BCR, is a potential immunotherapeutic target against autoimmune diseases. SM03 could disturb the CD22 homomultimeric configuration through disrupting cis binding to α2,6-linked sialic acids, induce rapid internalization of CD22 from the cell surface of human B cells, and facilitate trans binding between CD22 to human autologous cells. This in turn increased the activity of the downstream immunomodulatory molecule Src homology region 2 domain-containing phosphatase 1 (SHP-1) and decreased BCR-induced NF-κB activation in human B cells and B cell proliferation. This mechanism of action gives rationale to support the significant amelioration of disease and good safety profile in clinical trials, as by enabling the “self” recognition mechanism of CD22 via trans binding to α2,6 sialic acid ligands on autologous cells, SM03 specifically restores immune tolerance of B cells to host tissues without affecting the normal B cell immune response to pathogens.

Footnotes

  • This work was supported by SinoMab Bioscience Ltd.

  • The online version of this article contains supplemental material.

  • Received August 23, 2021.
  • Accepted March 8, 2022.
  • Copyright © 2022 by The American Association of Immunologists, Inc. 0022-1767/22/$37.50
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The Journal of Immunology: 209 (1)
The Journal of Immunology
Vol. 209, Issue 1
1 Jul 2022
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SM03, an Anti-CD22 Antibody, Converts Cis-to-Trans Ligand Binding of CD22 against α2,6-Linked Sialic Acid Glycans and Immunomodulates Systemic Autoimmune Diseases
Kin L. Wong, Zhengdong Li, Felix Ma, Dong Wang, Nan Song, Chi H. Chong, Ka K. Luk, Shui O. Leung
The Journal of Immunology June 10, 2021, ji2100820; DOI: 10.4049/jimmunol.2100820

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SM03, an Anti-CD22 Antibody, Converts Cis-to-Trans Ligand Binding of CD22 against α2,6-Linked Sialic Acid Glycans and Immunomodulates Systemic Autoimmune Diseases
Kin L. Wong, Zhengdong Li, Felix Ma, Dong Wang, Nan Song, Chi H. Chong, Ka K. Luk, Shui O. Leung
The Journal of Immunology June 10, 2021, ji2100820; DOI: 10.4049/jimmunol.2100820
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