What question did this study set out to answer?

The study aims to evaluate the efficacy and safety of a novel BCMA-targeting CAR T cell therapy (CT0590) in multiple myeloma patients.

June 13, 2026

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

Key Points

The study aims to evaluate the efficacy and safety of a novel BCMA-targeting CAR T cell therapy (CT0590) in multiple myeloma patients.
Conducted preclinical studies in vitro and in animal models to assess the CAR-NKG2A T cell effectiveness against NK cell attacks.
Executed a first-in-human phase I clinical trial (NCT05066022) enrolling five patients with relapsed and refractory multiple myeloma and primary plasma cell leukemia.
Monitored patient responses to therapy and evaluated safety outcomes including adverse events and toxicities.
Three out of five patients achieved confirmed responses, with two reaching stringent complete response (sCR).
The sCR in the patient with relapsed and refractory multiple myeloma lasted more than 23 months, while the sCR for the primary plasma cell leukemia patient lasted for 20 months.
Both responders exhibited robust expansion of uCAR T cells, with Cmax exceeding 280,000 copies/µg gDNA, and had higher baseline NKG2A expression on NK cells compared to nonresponders.

Abstract

Host-versus-graft reaction (HvGR) is a major challenge in allogeneic chimeric antigen receptor (CAR) T cell therapy. To counter host natural killer (NK) cell attacks, we armored allogeneic, human leukocyte antigen (HLA)-I deficient, B-cell maturation antigen (BCMA)-targeting CAR T cells with an NKG2A CAR. In vitro and animal studies demonstrated that allogeneic CAR-NKG2A T cells effectively resisted host NK cell-mediated killing. BCMA and NKG2A dual-targeting allogeneic CAR T cells (CT0590) resisted killing by NK cells and showed robust antitumor activity in preclinical in vivo models. On the basis of these data, a first-in-human study (NCT05066022) enrolled five patients (four with relapsed and refractory multiple myeloma RRMM and one with primary plasma cell leukemia pPCL). CT0590 was well-tolerated and caused no dose-limiting toxicities, treatment-related death, or graft-versus-host disease. Three patients achieved confirmed responses, including two with stringent complete response (sCR). Notably, sCR in the patient with RRMM was still ongoing (duration of response 23 months) at the time of data cutoff, and sCR in the patient with pPCL lasted for 20 months. Both patients showed robust expansion of universal CAR (uCAR) T cells (Cmax 280,000 copies/µg gDNA) and higher baseline NKG2A expression on NK cells than nonresponders. These results suggest that CAR-NKG2A technology may overcome HvGR, especially in patients with elevated NKG2A expression on NK cells. Further studies of CT0590 in RRMM and pPCL are warranted.

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