mRNA-encoding CD19-targeting T cell engager for refractory immune thrombocytopenia.

Wang, Mengyan; Liu, Tingting; Dai, Qihua; Teng, Jialin; Wu, Yaping; Jia, Jinchao; Meng, Jianfen; Ma, Yuning et al. · Cell · 2026

case_report · Level V

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Abstract

While T cell engagers (TCEs) and chimeric antigen receptor (CAR)-T cell therapy show clinical promise for B cell depletion, challenges regarding safety, efficacy, and durability persist. ABO2203 is a lipid nanoparticle-formulated messenger RNA (mRNA) encoding a CD19-targeting TCE. In transgenic mice, ABO2203 induced complete B cell depletion with attenuated cytokine release compared with TCE protein. In a first-in-human study involving three patients with refractory secondary immune thrombocytopenia, ABO2203 achieved rapid and complete peripheral B cell depletion, with sustained depletion in bone marrow. Patients exhibited durable platelet recovery, improved serology, and reduced disease activity through 6 months of follow-up. ABO2203 was well tolerated, presenting only grade 1 and 2 adverse events without cytokine release syndrome. B cell reconstitution was observed with predominant transitional and naive B cells. These findings establish mRNA-encoded TCEs as a potent and safer therapeutic modality for B cell-mediated autoimmune diseases.