An Integrated Polymeric mRNA Vaccine without Inflammation Side Effects for Cellular Immunity Mediated Cancer Therapy. Issue 3 (16th December 2022)

• Record Type: Journal Article
• Authors: Huang, Pei; Jiang, Lingsheng; Pan, Hui; Ding, Lingwen; Zhou, Bo; Zhao, Mengyao; Zou, Jianhua; Li, Benhao; Qi, Meiwei; Deng, Hongzhang; Zhou, Yongfeng; Chen, Xiaoyuan
• Is Part Of: Advanced materials. Volume 35:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-16
• Subjects: alternating copolymers -- cancer immunotherapy -- cellular immunity -- mRNA cancer vaccines -- polymer nanoparticles; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202207471
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: Among the few available mRNA delivery vehicles, lipid nanoparticles (LNPs) are the most clinically advanced but they require cumbersome four components and suffer from inflammation‐related side effects that should be minimized for safety. Yet, a certain level of proinflammatory responses and innate immune activation are required to evoke T‐cell immunity for mRNA cancer vaccination. To address these issues and develop potent yet low‐inflammatory mRNA cancer vaccine vectors, a series of alternating copolymers "PHTA" featured with ortho ‐hydroxy tertiary amine (HTA) repeating units for mRNA delivery is synthesized, which can play triple roles of condensing mRNA, enhancing the polymeric nanoparticle (PNP) stability, and prolonging circulation time. Unlike LNPs exhibiting high levels of inflammation, the PHTA‐based PNPs show negligible inflammatory side effects in vivo. Importantly, the top candidate PHTA‐C18 enables successful mRNA cancer vaccine delivery in vivo and leads to a robust CD8 + T cell mediated antitumor cellular immunity. Such PHTA‐based integrated PNP provides a potential approach for establishing mRNA cancer vaccines with good inflammatory safety profiles. Abstract : A series of alternating copolymers "PHTA" featured with ortho ‐hydroxy tertiary amine (HTA) repeat units is developed for mRNA cancer vaccine delivery. Such an integrated PHTA‐based polymeric nanoplatform shows negligible inflammatory side effects, and the top candidate PHTA‐C18 can successfully deliver mRNA cancer vaccine in vivo, leading to a robust CD8 + T cell mediated antitumor cellular immunity.