Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease

Immunopharmacol Immunotoxicol. 2021 Dec;43(6):666-673. doi: 10.1080/08923973.2021.1973493. Epub 2021 Sep 14.

Abstract

The pathogenic roles for B cells in autoimmunity include produce pathogenic autoantibodies and modulate immune responses via the production of cytokines and chemokines. The B lymphocyte stimulator BLyS (also known as B-cell-activating factor, BAFF) and APRIL (a proliferation-inducing ligand) are critical factors in the maintenance of the B-cell pool and humoral immunity, namely BLyS modulates the differentiation and maturation of immature B cell, while APRIL modulates the function and survival of long-lived plasma cell, which plays a prominent role in the pathogenesis of autoimmune diseases. Telitacicept is a novel recombinant fusion protein of both the ligand-binding domain of the TACI receptor and the Fc component of human IgG and which is a BLyS/APRIL dual inhibitor. Moreover, telitacicept was developed by Remegen Co., Ltd. in China and is approved to treat systemic lupus erythematosus in China. We review the rationale, clinical evidence, and future perspectives of telitacicept for the treatment of autoimmune disease.HighlightThe B lymphocyte stimulator BLyS (also known as B-cell-activating factor, BAFF) and APRIL (a proliferation-inducing ligand), members of tumor necrosis factor (TNF) family, and which are critical factors in the maintenance of the B-cell pool and humoral immunity.BAFF and APRIL are implicated in the pathogenesis of several human autoimmune diseases with autoreactive B-cell involvement, and targeting both is beneficial for the treatment of autoimmune diseases.Telitacicept is a novel recombinant fusion protein of both the ligand-binding domain of the TACI receptor and the Fc component of human IgG, as a BLyS/APRIL dual inhibitor and which has been approved by National Medical Products Administration (MNPA) for the treatment of patients with SLE in China.With more clinical trials underway, telitacicept may also be approved for the treatment of other autoimmune diseases in the future.

Keywords: APRIL; BLyS; autoimmune disease; telitacicept.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • B-Cell Activating Factor / antagonists & inhibitors*
  • B-Cell Activating Factor / immunology
  • Clinical Trials as Topic / methods
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / antagonists & inhibitors*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology

Substances

  • B-Cell Activating Factor
  • Immunosuppressive Agents
  • Recombinant Fusion Proteins
  • TNFSF13B protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • TACI receptor-IgG Fc fragment fusion protein