Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity

Cancer Res. 2010 Nov 15;70(22):9031-40. doi: 10.1158/0008-5472.CAN-10-0699. Epub 2010 Nov 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / genetics*
  • Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytotoxicity, Immunologic / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Immunization / methods
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / prevention & control
  • RNA / administration & dosage
  • RNA / immunology*
  • Survival Analysis


  • Antigens
  • Cancer Vaccines
  • RNA