Vitalina Dzutseva: Could mRNA Encoded TCEs Transform B Cell Depletion?
Vitalina Dzutseva, Senior Medical Director, GPS, Cell and Gene Therapy at AstraZeneca, shared a post on LinkedIn about a recent article by Mengyan Wang et al., published in Cell Press, adding:
“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.”
Title: mRNA-encoding CD19-targeting T cell engager for refractory immune thrombocytopenia
Authors: Mengyan Wang, Tingting Liu, Qihua Dai, Jialin Teng, Yaping Wu, Jinchao Jia, Jianfen Meng, Yuning Ma, Hui Shi, Xiaobing Cheng, Honglei Liu, Yutong Su, Junna Ye, Huihui Chi, Zhuochao Zhou, Yue Sun, Yan Wu, Jia Chen, Wei Yin, Peng Gao, Wenjie Song, Rui Lin, Bo Ying, Chengde Yang, Qiongyi Hu
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