SLE Preview: advances to achieve deep B-cell depletion Save

The race is on for the first chimeric antigen receptor (CAR)-based therapy to be approved for the treatment of systemic lupus erythematosus (SLE). Its main principle is to induce deep B-cell depletion, with the hope to reset the B-cell aberrant immunity for a sustained clinical remission.

At EULAR 2025 in Barcelona, several advances of CAR-based therapies will be presented. When interpreting these data, key aspects to be considered include a) immune cells modified to fight autoreactive B-cells (e.g. T-cells or NK cells); b) target antigens (e.g. CD19 or BCMA); c) cell source (e.g. patient’s own – autologous or donor’s cells – allogeneic); d) manufacturing (time- and cost-consuming or “off-the-shelf”), e) efficacy, f) safety (e.g. cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and the risk of secondary T-cell cancer) and g) patient population studied.

Selected studies to be presented include off-the-shelf CAR-T derived from a clonal master cell bank engineered from an induced pluripotent stem cell (iPSC) line by Dr Sandhu et al. (OP0032), Dual CD19/BCMA CAR-T developed on the novel FasTCAR-T platform with next-day manufacturing by Dr Fu et al. (OP0074), a rapidly manufactured, autologous CD19 CAR-T therapy, rapcabtagene autoleucel by Dr Morand et el. (OP0079), a fully human, autologous 4-1BB anti-CD19-CAR T cell therapy, designed to deeply and transiently deplete CD19 +ve cells following a weight-based one-time infusion by Dr Sheikh et al. (OP0202), and allogenic CD19 CAR NK cell by Dr Gao et al. (LB0009).

In addition to CAR-based therapies, CD19 targeted bi-specific T-cell engagers (BiTE) have the potential to induce B-cell depletion with potential better safety than CAR-based therapy and off-the-shelf convenience. However, efficacy could be limited by T-cell dysfunction or exhaustion. To overcome this, Dr Huang et al. (LB0007) will present preliminary results on a first-in-class anti-CD19, anti-CD3, anti-CD28 tri-specific antibody, CC312, that leads to redierected T-cell cytotoxicity towards CD19-positive autoreactive B-cells.

A deep and durable state of B-cell depletion can be achieved by using a novel type 2 anti-CD20 mAb, obinutuzumab. Dr Rovin et al. (OP0006) will present post-hoc analysis of REGENCY Phase 3 RCT in lupus nephritis at Week 76. This study will assess whether superiority of obinutuzumab plus standard therapy over placebo plus standard therapy is consistent across various renal response definitions used in belimumab and voclosporin trials.