Overview of CAR T-cell therapy in the management of systemic lupus erythematosus

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.

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

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 

Key learnings

The interim findings from ongoing clinical trials of CAR T-cell therapy in lupus showed: favorable safety, CAR T-cell expansion, B-cell depletion, and efficacy with rapcabtagene autoleucel in patients with srSLE; immune reset, eliminated autoantibodies, and a sustained drug-free remission with B-cell maturation antigen-cluster of differentiation 19 (BCMA-CD19) compound CAR in patients with SLE and lupus nephritis; and positive outcomes in the first patient with lupus nephritis enrolled in the KYV-101 trial. A compassionate use program showed abrogated disease, eliminated autoantibodies, and drug-free remission with MB-CART 19.1.