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Overview of CAR T-cell therapy in the management of systemic lupus erythematosus
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Systemic lupus erythematosus (SLE) is characterized by autoreactive B cells producing autoantibodies against self-antigens, with some patients developing severe, refractory SLE (srSLE).1,2 For such cases, chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising novel treatment option.1 The process of CAR T-cell treatment is depicted in Figure 1.
Figure 1. Procedure of CAR T-cell treatment in SLE*
CAR, chimeric antigen receptor; SLE, systemic lupus erythematosus.
*Adapted from Lin, et al.1 Created with BioRender.com
Currently, there is a lack of clinical experience with CAR T-cell therapy in patients with SLE. In Figure 2, we summarize the ongoing clinical trials investigating various CAR T-cell therapies and a case series involving patients with srSLE in a compassionate use program.2-5
Figure 2. Overview of CAR T-cell therapies under investigation for management of SLE*
CAR, chimeric antigen receptor; CRS, cytokine release syndrome; cCAR, compound CAR; ds, double-stranded; ICANS, immune effector-cell associated neurotoxicity; Ig, immunoglobulin; LLDAS, Lupus Low Disease Activity State; LN, lupus nephritis; phGA, Physician Global Assessment; SAE, serious adverse event; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index.
*Data from Cortés Hernández, et al.2; Yuan, et al.3; PR Newswire.4; Taubmann, et al.5
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- Lin CJ, Lee YH, Shih PC, et al. From concept to reality: CAR-T therapy as a glimmer of hope for systemic lupus erythematosus patients. Int J Rheum Dis. 2023;26(11):2137-2140. DOI: 1111/1756-185X.14871
- Cortés Hernández J, Barba P, Linares Alberich M, et al. An open-label, multicenter, phase 1/2 study to assess safety, efficacy and cellular kinetics of YTB323, a rapid manufacturing CAR-T cell therapy targeting CD19 on B cells, for severe refractory systemic lupus erythematosus: Preliminary results. Abstract #L13. American College of Rheumatology annual meeting (ACR Convergence) 2023; Nov 10-15, 2023; San Diego, US.
- Yuan Y, He S, Zhang W, et al. Novel BCMA-CD19 compound CAR-T (cCAR) targets B cells and plasma cells achieving immune reset and eliminates all autoantibodies in systemic lupus erythematosus (SLE) and lupus nephritis (LN) patients resulting in long-term, medication-free remission. Abstract #1493. American College of Rheumatology annual meeting (ACR Convergence) 2023; Nov 10-15, 2023; San Diego, US.
- milestone for first U.S. patient dosed in phase 1 clinical trial of CD19 CAR T-cell therapy for lupus nephritis. https://www.prnewswire.com/news-releases/kyverna-therapeutics-announces-achievement-of-28-day-post-infusion-milestone-for-first-us-patient-dosed-in-phase-1-clinical-trial-of-cd19-car-t-cell-therapy-for-lupus-nephritis-301925488.html. Published Sep 13, 2023. Accessed Dec 4, 2023.
- Taubmann J, Müller F, Boeltz S, et al. Long term safety and efficacy of car-t cell treatment in refractory systemic lupus erythematosus - data from the first seven patients. Oral abstract #OP0141. European Alliance of Associations for Rheumatology Congress 2023; May 31-June 3, 2023; Milan, IT.
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