A novel triple-knockout allogeneic BCMA CAR T-cell therapy (CT0590) for multiple myeloma: preclinical and phase 1 study.

Allogeneic BCMA CAR T cells armed with NKG2A receptor (CT0590) effectively resist host NK cell attacks and show durable responses in multiple myeloma patients.

• Why it matters: Overcoming host-versus-graft reaction (HVGR) remains a key challenge in allogeneic CAR T-cell therapy, limiting treatment efficacy and safety for patients with blood cancers.
• What they did: Researchers engineered HLA-I-deficient BCMA-targeting CAR T cells with an NKG2A receptor and tested them through in vitro, animal, and a phase 1 clinical trial involving five patients, including those with relapsed/refractory multiple myeloma and primary plasma cell leukemia.
• The result: CT0590 was well tolerated, with three patients achieving confirmed responses—two with stringent complete responses lasting over 20 months—indicating that CAR-NKG2A technology may effectively overcome HVGR and improve outcomes in high NKG2A-expressing patients.