Adicet's Off-the-Shelf CAR-T prula-cel Drives Lupus Remissions in Phase 1, With No IEC-HS or ICANS
核心洞察
Adicet Bio reported that 54% of 22 efficacy-evaluable lupus patients achieved DORIS remission at 12 months after a single dose of allogeneic gamma delta CAR-T prula-cel.
Half of evaluable lupus nephritis (搜索) patients achieved a complete renal response at 12 months, and all patients stopped immunosuppressants while all but one cut steroids to 5 mg or less.
No IEC-HS, ICANS, dose-limiting toxicities or graft-versus-host disease occurred, and no cytokine release syndrome above Grade 2 was reported across 24 safety-evaluable patients.
Adicet Bio has reported Phase 1 data showing that its investigational allogeneic gamma delta CAR-T therapy prulacabtagene leucel (搜索), or prula-cel, produced durable remissions in patients with systemic lupus erythematosus (搜索) (SLE) with or without lupus nephritis (搜索), without the hyperinflammatory toxicities that have disrupted other CD19 (搜索)-directed autoimmune CAR-T programs.
The data cutoff was August 28, 2026, and covered 22 efficacy-evaluable patients: 16 with lupus nephritis (搜索) and six with extra-renal SLE. Follow-up ranged from six to 21 months. All patients had previously received at least three therapies, and 71% had received four or more.
Remission and Renal Response at 12 Months
At 12 months, 54% of evaluable patients achieved DORIS remission, according to the company. Among evaluable patients with lupus nephritis (搜索), 50% achieved a complete renal response at 12 months.
The remissions followed a single dose of prula-cel in patients who had failed multiple prior therapies, said Lloyd Klickstein, M.D., Ph.D., Adicet's interim chief medical officer. "Notably, these remissions were achieved off immunosuppression and were accompanied by biological evidence of an immune reset," Klickstein said in a release.
All patients discontinued immunosuppressants, and all but one reduced background steroid treatment to 5 mg or less of prednisone equivalent per day.
B-Cell Depletion and Immune Reset
All 22 efficacy-evaluable patients achieved undetectable levels of CD19 (搜索)+ B cells, followed by naive-dominant B-cell reconstitution. Reductions in anti-dsDNA antibodies were observed in 91% of patients who were positive for the antibodies at baseline.
Prula-cel targets CD20 (搜索) expressed on B cells, the antibody-producing immune cells that go rogue in autoimmune diseases such as lupus. Adicet is seeing early signs that the therapy resets the immune system, with newly created B cells not showing signs of causing disease.
"The B cells that come back after this reset, they come as naive B cells," Adicet CEO Chen Schor told Fierce Biotech. "These are B cells that are not associated with the disease, and that is really the definition of a reset."
Unlike other CAR-T cell therapies, prula-cel consists of an uncommon subtype of T cells called gamma delta T cells, which naturally reside in the body's tissues rather than circulating in the bloodstream. "That makes them potentially very favorable for autoimmune diseases because, at the end of the day, the disease happens in the organs," Schor said.
Safety Profile Across 24 Patients
The safety analysis included 24 evaluable patients. No cytokine release syndrome (CRS) above Grade 2 was reported; Grade 1 or Grade 2 CRS occurred in 25% of patients. Adicet reported no cases of immune effector cell-associated hemophagocytic syndrome (IEC-HS), immune effector cell-associated neurotoxicity syndrome (ICANS), dose-limiting toxicities or graft-versus-host disease.
Infections were reported in 54% of safety-evaluable patients, with Grade 3 or higher infections in 8.3%.
The absence of IEC-HS contrasts with recent setbacks in the field. Novartis' autoimmune program for the CD19 (搜索)-targeted CAR-T candidate rap-cel (搜索) recorded three deaths from IEC-HS, and Bristol Myers Squibb (搜索) recently paused trials of its CD19-targeted CAR-T zola-cel (搜索) due to "transient and reversible inflammatory events." Both rap-cel and zola-cel are autologous, derived from patients rather than being off-the-shelf like prula-cel.
According to Adicet, the U.S. Food and Drug Administration has aligned with the company on outpatient administration based on the reported safety profile.
Pivotal Lupus Nephritis Study Planned
Adicet plans to begin start-up activities for a pivotal single-arm study of prula-cel in patients with lupus nephritis (搜索) during the fourth quarter of 2026. The planned study will use complete renal response at 12 months as its primary endpoint.
The company also plans to discuss with the FDA a potential expansion of the pivotal study to include lupus patients without nephritis, citing the DORIS remission rate observed in the Phase 1 study. Adicet expects to provide a clinical data update in systemic sclerosis (搜索) during the first half of 2027, followed by an additional lupus nephritis (搜索) and SLE data update by mid-2027.
Adicet intends to develop prula-cel as a one-and-done treatment option for lupus rather than relying on a cocktail of therapies. Autoimmune diseases have become a major next frontier for CAR-T, with multiple therapies already approved for blood cancers. A first approval in the space is likely coming soon, with Kyverna Therapeutics' candidate for stiff-person syndrome (搜索) currently undergoing a rolling submission to the FDA that should wrap up by the end of the year.
Similar to the debut of drugs targeting tumor necrosis factor more than 20 years ago, Schor said, "this might be a new era in autoimmune diseases."