Intravenous Delivery of RNA Encoding Anti-PD-1 Human Monoclonal Antibody for Treating Intestinal Cancer
Lipei Wu, Weiwei Wang, Jiale Tian, Chunrun Qi, Zhengxin Cai, Wenhui Yan, Shihai Xuan, Anquan Shang
Abstract
delivery and protect mRNA from degradation. Intravenously delivered the single dose of mRNA-LNPs in mice resulted in duration of serum Pembrolizumab level over 25 μg/mL more than 35 days. Pharmacokinetic study exhibited significantly enhanced drug exposure of mRNA-encoded mAbs compared with direct injection of Pembrolizumab at same dose. Chronic treatment of the tumor-bearing mice with LNP-encapsulated Pembrolizumab mRNA effectively downregulated the growth of intestinal tumors and improved the animal survival. In brief, our present research demonstrated that the application of LNP-encapsulated IVT-mRNA can change the human body into a protein drug manufacturing site to express full-size mAbs for treating cancer and hold potential to be a novel alternative to protein-based therapies.