Targeting the CD40-CD154 Signaling Pathway for Treatment of Autoimmune Arthritis
Abstract
:1. Introduction
2. CD154 and the CD40-CD154 Interaction
3. CD40 and CD40-Mediated Signaling
4. The CD40-CD154 Interaction in the Pathogenesis of Autoimmune Disorders
5. Clinical Analyses of Blocking the CD40-CD154 Axis in Humans
5.1. Anti-CD154
5.2. Anti-CD40
6. Perspectives
Funding
Acknowledgments
Conflicts of Interest
References
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Aimed Target | Drugs | Structure | Aimed Diseases | Trial Designs | Patient No./Study Period | Results and Comments | Ref. |
---|---|---|---|---|---|---|---|
CD154 | IDEC-131 | Humanized mAb | SLE * | Phase I & Phase II, DB, PC | 23/3 months and 85/7 months | Safe and well-tolerated and no clinical benefits compared to baseline | [91,92] |
CD154 | BG9588 | Humanized mAb | SLE (PLN) | phase II, open-label | 28/22–24 wks | Early termination of the trial due to thromboembolic AE although clinical benefits noted | [93] |
CD154 | Dapirolizumab pegol | Fab | SLE | Phase I, DB & Phase IIb, DB, PC | 16/12 wks and 182/24 wks | Clinical benefits in high disease activity group at baseline & Fail to meet the primary endpoint (noted in press release) | [94,95,96] |
CD154 | VIB4920 (MEDI4920) | Tn3 fusion protein | RA | Phase Ib, DB, PC | 57/12 wks | Significant benefits in clinical and laboratorial assessment | [97] |
CD40 | CFZ533 | Humanized mAb | SS; RA | Phase IIa, DB, PC & Phase I, DB, PC | 44/12 wks and 75/20 wks (estimated) | Clinical benefits in SS patients & The drug was well-tolerated in RA patients | [18,98], NCT02-089087 |
CD40 | BI 655064 | Humanized mAb | RA, fail with MTX | Phase IIa, DB, PC | 67/12 wks | Improvement in laboratorial parameters but no significant clinical efficacy | [99] |
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Lai, J.-H.; Luo, S.-F.; Ho, L.-J. Targeting the CD40-CD154 Signaling Pathway for Treatment of Autoimmune Arthritis. Cells 2019, 8, 927. https://doi.org/10.3390/cells8080927
Lai J-H, Luo S-F, Ho L-J. Targeting the CD40-CD154 Signaling Pathway for Treatment of Autoimmune Arthritis. Cells. 2019; 8(8):927. https://doi.org/10.3390/cells8080927
Chicago/Turabian StyleLai, Jenn-Haung, Shue-Fen Luo, and Ling-Jun Ho. 2019. "Targeting the CD40-CD154 Signaling Pathway for Treatment of Autoimmune Arthritis" Cells 8, no. 8: 927. https://doi.org/10.3390/cells8080927