Advanced Science (Jan 2023)

Lipid Nanoparticle Delivery System for mRNA Encoding B7H3‐redirected Bispecific Antibody Displays Potent Antitumor Effects on Malignant Tumors

  • Cheng Huang,
  • Xing Duan,
  • Jichao Wang,
  • Qingqing Tian,
  • Yangmei Ren,
  • Kepan Chen,
  • Zongliang Zhang,
  • Yuanyou Li,
  • Yunyu Feng,
  • Kunhong Zhong,
  • Yuelong Wang,
  • Liangxue Zhou,
  • Gang Guo,
  • Xiangrong Song,
  • Aiping Tong

DOI
https://doi.org/10.1002/advs.202205532
Journal volume & issue
Vol. 10, no. 3
pp. n/a – n/a

Abstract

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Abstract The therapeutic use of bispecific T‐cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half‐life of BiTE have dampened some of the promise and impeded the pace of BiTE‐based therapeutics to combat diseases. Nowadays, in vitro‐transcribed mRNA has achieved programmed production, which is more flexible and cost‐effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE‐based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA‐LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half‐life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects.

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