1. Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity.
- Author
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Mai Y, Guo J, Zhao Y, Ma S, Hou Y, and Yang J
- Subjects
- Administration, Intranasal, Animals, Carcinoma, Lewis Lung, Cell Differentiation, Fatty Acids, Monounsaturated chemistry, Female, Humans, Liposomes chemistry, Lung Neoplasms immunology, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Neoplasm Transplantation, Protamines chemistry, Quaternary Ammonium Compounds chemistry, RNA, Messenger chemistry, RNA, Messenger genetics, Tumor Burden, Cancer Vaccines immunology, Dendritic Cells immunology, Immunotherapy methods, Keratin-19 genetics, Liposomes immunology, Lung Neoplasms therapy, RNA, Messenger immunology
- Abstract
Immunization with synthetic mRNA encoding tumor-associated antigens is an emerging vaccine strategy for the treatment of cancer. In order to prevent mRNA degradation, promote antigen-presenting cells antigen presentation, and induce an anti-tumor immune response, we investigated the nasal administration of mRNA vaccines with positively charged protamine to concentrate mRNA, form a stable polycation-mRNA complex, and encapsulate the complex with DOTAP/Chol/DSPE-PEG cationic liposomes. Cationic liposome/protamine complex (LPC) showed significantly greater efficiency in uptake of vaccine particles in vitro and stronger capacities to stimulate dendritic cell maturation, which further induced a potent anti-tumor immune response. Intranasal immunization of mice with cationic LPC containing mRNA encoding cytokeratin 19 provoked a strong cellular immune response and slowed tumor growth in an aggressive Lewis lung cancer model. The results of this study provide evidence that cationic LPC can be used as a safe and effective adjuvant and this mRNA formulation provides a basis for anti-cancer vaccination of humans., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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