Ultrasound Responsive Nanovaccine Armed with Engineered Cancer Cell Membrane and RNA to Prevent Foreseeable Metastasis

• Published in: Advanced science 2023-07, Vol.10 (19), p.e2301107-n/a
• Main Authors: Sun, Wenqi, Ji, Panpan, Zhou, Tian, Li, Zhelong, Xing, Changyang, Zhang, Liang, Wei, Mengying, Yang, Guodong, Yuan, Lijun
• Format: Article
• Language: English
• Subjects: alternative splicing; Animals; Antigen Presentation; Antigens, Neoplasm - metabolism; Breast cancer; Cancer therapies; cancer vaccine; Cancer Vaccines; Cell Membrane - metabolism; Cells; Dendritic Cells; Efficiency; Immune system; Lymphatic system; Lymphocytes; Melanoma; Metastasis; Mice; Microscopy; Mutation; Nanoparticles; Neoplasms - metabolism; Neoplasms - therapy; Polylactic Acid-Polyglycolic Acid Copolymer - metabolism; Proteins; RNA - metabolism; sonosensitizer; Ultrasonic imaging
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202301107

Cancer vaccine has been considered as a promising immunotherapy by inducing specific anti‐tumor immune response. Rational vaccination at suitable time to efficiently present tumor associated antigen will boost tumor immunity and is badly needed. Here, a poly (lactic‐co‐glycolic acid) (PLGA)‐based cancer vaccine of nanoscale is designed, in which engineered tumor cell membrane proteins, mRNAs, and sonosensitizer chlorin e6 (Ce6) are encapsulated at high efficiency. The nanosized vaccine can be efficiently delivered into antigen presentation cells (APCs) in lymph nodes after subcutaneous injection. In the APCs, the encapsulated cell membrane and RNA from engineered cells, which have disturbed splicing resembling the metastatic cells, provide neoantigens of metastatic cancer in advance. Moreover, the sonosensitizer Ce6 together with ultrasound irradiation promotes mRNA escape from endosome, and augments antigen presentation. Through 4T1 syngeneic mouse model, it has been proved that the proposed nanovaccine is efficient to elicit antitumor immunity and thus prevent cancer metastasis. The designed nanosized cancer vaccine, in which cell membrane proteins and RNAs from engineered cells with splicing disturbed, and sonosensitizer Ce6 are encapsulated into the PLGA‐based nanoparticles, could be efficiently delivered into lymph nodes. Assisted by ultrasound irradiation, the vaccine elicits strong immune response to inhibit tumor growth and prevent metastasis.