2010/11/07 by Sebastian Kreiter, Abderraouf Selmi, Mustafa Diken +5 · 2 citations
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Immunotherapy and Immune Responses #RNA Interference and Gene Delivery #vaccines and immunoinformatics approaches
paper · pdf · doi:10.1158/0008-5472.can-10-0699
openalex publication_date 2010/11/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Although naked antigen-encoding RNA has entered clinical testing, basic knowledge on how to apply this promising novel vaccine format is still pending. By comparing different administration routes, we observed surprisingly potent antigen-specific T-cell immunity upon intranodal injection of naked antigen-encoding RNA. RNA was selectively uptaken by resident dendritic cells, propagated a T-cell attracting and stimulatory intralymphatic milieu, and led to efficient expansion of antigen-specific CD8+ as well as CD4+ T cells. By intranodal treatment of mice with repeated cycles of RNA, we achieved de novo priming of naïve T cells, which became potent cytolytic effectors capable of homing to primary and secondary lymphatic tissues as well as memory T cells. In tumor-bearing mice intralymphatic RNA vaccination elicited protective and therapeutic antitumor immune responses, resulting in a remarkable survival benefit as compared with other treatment regimens. This is the first report of strong systemic antigen-specific Th1-type immunity and cancer cure achieved with naked antigen-encoding RNA in preclinical animal models.