Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity.

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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Mai Y,Guo J,Zhao Y,Ma S,Hou Y,Yang J

doi

10.1016/j.cellimm.2020.104143

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

104143

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(20)30303-8

journal_volume

354

pub_type

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