Therapeutic tactics for targeting B lymphocytes in autoimmunity and cancer

Eur J Immunol. 2024 Jan;54(1):e2249947. doi: 10.1002/eji.202249947. Epub 2023 Oct 20.

Abstract

B lymphocytes have become a very popular therapeutic target in a number of autoimmune indications due to their newly appreciated roles, and approachability, in these diseases. Many of the therapies now applied in autoimmunity were initially developed to deplete malignant B cells. These strategies have also been found to benefit patients suffering from such autoimmune diseases as multiple sclerosis, type I diabetes, systemic lupus erythematosus, and rheumatoid arthritis, to name a few. These observations have supported the expansion of research addressing the mechanistic contributions of B cells in these diseases, as well as blossoming of therapeutics that target them. This review seeks to summarize cutting-edge modalities for targeting B cells, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, chimeric antigen receptor-T cells, and small molecule inhibitors. Efforts to refine B-cell targeted therapy to eliminate only pathogenic autoreactive cells will be addressed as well as the potential for future B-cell-based cellular therapeutics. Finally, we also address approaches that seek to silence B-cell function without depletion.

Keywords: Autoimmune disease; B-cell malignancy; B-cell targeted therapies; CAR T cells; Monoclonal antibodies.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Autoimmune Diseases*
  • Autoimmunity
  • B-Lymphocytes
  • Humans
  • Neoplasms* / drug therapy

Substances

  • Antibodies, Monoclonal