FT819 Remodels Lupus B Cells in Clinical Trial

FT819 is a gene-edited, induced pluripotent stem cell-derived anti-CD19 CAR T-cell product designed for off-the-shelf use in autoimmune disease. Fate Therapeutics has previously described the platform as CRISPR-engineered, with targeted insertion of the CAR construct into the TRAC locus and bi-allelic disruption of endogenous TCR expression to prevent graft-versus-host disease. In the ongoing Phase 1 study, patients with moderate-to-severe SLE received a single infusion while remaining on background immunosuppressive therapy and without lymphodepleting conditioning chemotherapy.

Newly presented ASGCT data showed that all three evaluable patients achieved SRI-4 responses – a composite endpoint requiring at least a four-point improvement in SLE disease activity without worsening in other clinical measures – while two of three reached a lupus low disease activity state (LLDAS). Earlier analyses had already shown reductions in SLEDAI scores, physician global assessment and fatigue, with no reported CRS, ICANS or graft-versus-host disease.

Mechanistic analyses focused on B-cell depletion and repertoire remodelling. Earlier translational data demonstrated 47–73% peripheral B-cell depletion, along with depletion of B cells in secondary lymphoid tissue, after treatment without conditioning chemotherapy. The updated dataset extends these findings, reporting depletion of dominant B-cell receptor clones averaging 79%, with effects persisting for up to 12 months. Previous sequencing analyses had also shown contraction of expanded class-switched B-cell populations and restoration of BCR diversity towards a more naïve profile.

Together, the new data support the idea that FT819 can drive sustained immune resetting without conventional conditioning regimens. Fate Therapeutics also announced the initiation of dose level 2 testing at 900 million cells.

The study was conducted by Trever Greene and colleagues from Fate Therapeutics in collaboration with the University of Nebraska Medical Center, Providence Medical Foundation and the University of Minnesota. The updated results were presented in a press release on 11 May.