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用 B 细胞成熟抗原/CD3 双特异性抗体编码质粒 DNA 的基因治疗治疗多发性骨髓瘤。

Gene therapy with B-cell maturation antigen/CD3 bispecific antibody encoding plasmid DNA for treating multiple myeloma.

机构信息

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.

State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, China.

出版信息

Br J Haematol. 2023 May;201(3):417-421. doi: 10.1111/bjh.18230. Epub 2022 May 20.

Abstract

The delivery of bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA) and CD3 using the gene therapy approach is a promising alternative for BsAb administration in patients with multiple myeloma (MM). In the present study, we evaluated the efficacy of this approach using a xenograft model. Tumour growth was significantly delayed in mice treated with single electroporation-enhanced intramuscular injection of plasmid DNA encoding BCMA/CD3 BsAb in contrast to the vehicle control-treated group. Limited toxicity was observed following treatment. This study demonstrates that the gene therapy-based approach for the delivery of BCMA/CD3 BsAb is effective and safe for the treatment of MM.

摘要

采用基因治疗方法递送针对 B 细胞成熟抗原(BCMA)和 CD3 的双特异性抗体(BsAbs),为多发性骨髓瘤(MM)患者的 BsAb 给药提供了一种很有前途的替代方法。在本研究中,我们使用异种移植模型评估了这种方法的疗效。与载体对照组相比,用编码 BCMA/CD3 BsAb 的质粒 DNA 进行单次电穿孔增强肌内注射治疗的小鼠,肿瘤生长明显延迟。治疗后观察到有限的毒性。这项研究表明,用于递送 BCMA/CD3 BsAb 的基于基因治疗的方法对于 MM 的治疗是有效且安全的。

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