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

• DOI: 10.1002/advs.202205532
• Publication Date: 2022-11-20T16:51:06Z
• Authors: 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
• Keywords: Bispecific antibody; Delivery system

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