Citation

Yu H, Wu M, Zhao N, Dong M, Wang Y, Yu K, Sun C, Xu N, Ge L, Liu W. Toxicol. Lett. 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Elsevier Publishing)

DOI

10.1016/j.toxlet.2023.06.008

PMID

37390852

Abstract

DNA-encoded monoclonal antibodies (DMAbs) and in vivo expression of antibody therapeutics presents an innovative alternative to conventional delivery methods. Therefore, in order to prevent the lethal dose of ricin toxin (RT) and to avoid human anti-mouse antibody (HAMA) reaction, we developed the human neutralizing antibody 4-4E against RT and constructed DMAb-4-4E. The human neutralizing antibody 4-4E could neutralize RT in vitro and in vivo, while the mice in RT group all died. Using intramuscular electroporation (IM EP), antibodies were rapidly expressed in vivo within 7 days and were enriched in intestine and gastrocnemius muscle mostly. Besides, we found that DMAbs have shown a broad protective efficacy of RT poisoning prophylaxis. Driven by plasmids for IgG expression, mice were survived and the blood glucose level of mice in DMAb-IgG group returned to normal at 72h post RT challenge, and the RT group died within 48h. Furthermore, hindrance of protein disulfide isomerase (PDI) and accumulation of RT in endosomes were found in IgG-protected cells, revealing the possible mechanism of neutralization details. These data support the further study of RT-neutralizing monoclonal antibodies (mAbs) in the development.

Language: en

Keywords

DNA-encoded monoclonal antibodies; human antibody; Ricin toxin