Lupus (Systemic Lupus Erythematosus)

A systemic autoimmune disease. Central case study for the immune reset paradigm at SDDS 2026.

CAR-T for Lupus

• Georg Schett & Fabian Müller (Erlangen): refractory SLE patients treated with CD19 4-1BBζ CAR-T — dramatic improvement, immunosuppression discontinued
• Schett’s landmark NEJM case series: 7 patients entering complete remission
• Longest ongoing remission: >3 years, drug-free (June, Session V)
• ~300 CAR-T trials for autoimmunity now active

Other Approaches

• Robert Plenge (BMS): registrational CD19 CAR-T trial based on Schett’s series (Session IX)
• Gilead: gamgertamig (BCMAx CD3 T-cell engager) for autoimmune indications
• Tom Hudson (Versant): B-cell depletion’s outsized impact in lupus “rewired his thinking” — bet on cells, not pathways (Session III)

Mechanism

Not classical immunosuppression — immune reset: complete B-cell ablation followed by naive B-cell repopulation. B-cell aplasia (the on-target side effect tolerated in oncology) is now the therapeutic mechanism.