Monoclonal antibodies and fusion proteins and their complications: Targeting B cells in autoimmune diseases Susan Lee, MD, Mark Ballow, MD Journal of.

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Presentation transcript:

Monoclonal antibodies and fusion proteins and their complications: Targeting B cells in autoimmune diseases Susan Lee, MD, Mark Ballow, MD Journal of Allergy and Clinical Immunology Volume 125, Issue 4, Pages 814-820 (April 2010) DOI: 10.1016/j.jaci.2010.02.025 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 B cell–targeted therapy with mAbs and fusion receptor proteins. The 2 principal targets on B cells are CD20 and CD22. CD20 was the first B-cell surface molecule targeted for B cell–directed therapy with mAbs, eg, rituximab. More recently, second-generation and third-generation anti-CD20 mAbs that are humanized (ocrelizumab and veltuzumab) and fully human (ofatumumab) are in clinical trials. Epratuzumab is a humanized mAb directed at CD22. BAFF (B-lymphocyte stimulator; BLyS) and APRIL are important survival and growth factors for B cells that are potential targets in autoimmune diseases. BAFF and APRIL interact with 3 different receptors on B cells: BAFF-R, TACI, and BCMA. Belimumab is a human mAb that binds soluble BAFF, preventing the binding to the BAFF-R. BR3-Fc is a BAFF-R fusion protein linked to the Fc domain of IgG that binds BAFF. Atacicept (TACI-Ig) is a fusion protein that binds both BAFF and APRIL growth factors. Tocilizumab is a humanized anti–IL-6 receptor mAb that blocks the action of IL-6, an important cytokine in the terminal differentiation of B cells and inflammatory processes. BCR, B cell receptor; sIgM/sIgD, etc, soluble IgM/IgD, etc; Blimp-1, B lymphocyte-induced maturation protein-1; IRF-4, interferon regulatory factor-4; MILF, microphthalmia-associated transcription factor; Pax-5, paired box-5; XBP-1, X-box binding protein-1. Journal of Allergy and Clinical Immunology 2010 125, 814-820DOI: (10.1016/j.jaci.2010.02.025) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions