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A liposomal RNA vaccine inducing neoantigen-specific CD4+T cells augments the antitumor activity of local radiotherapy in mice
- Source :
- OncoImmunology; January 2020, Vol. 9 Issue: 1
- Publication Year :
- 2020
-
Abstract
- ABSTRACTAntigen-encoding, lipoplex-formulated RNA (RNA-LPX) enables systemic delivery to lymphoid compartments and selective expression in resident antigen-presenting cells. We report here that the rejection of CT26 tumors, mediated by local radiotherapy (LRT), is further augmented in a CD8+T cell-dependent manner by an RNA-LPX vaccine that encodes CD4+T cell-recognized neoantigens (CD4 neoantigen vaccine). Whereas CD8+T cells induced by LRT alone were primarily directed against the immunodominant gp70 antigen, mice treated with LRT plus the CD4 neoantigen vaccine rejected gp70-negative tumors and were protected from rechallenge with these tumors, indicating a potent poly-antigenic CD8+T cell response and T cell memory. In the spleens of CD4 neoantigen-vaccinated mice, we found a high number of activated, poly-functional, Th1-like CD4+T cells against ME1, the immunodominant CD4 neoantigen within the poly-neoantigen vaccine. LRT itself strongly increased CD8+T cell numbers and clonal expansion. However, tumor infiltrates of mice treated with CD4 neoantigen vaccine/LRT, as compared to LRT alone, displayed a higher fraction of activated gp70-specific CD8+T cells, lower PD-1/LAG-3 expression and contained ME1-specific IFNγ+CD4+T cells capable of providing cognate help. CD4 neoantigen vaccine/LRT treatment followed by anti-CTLA-4 antibody therapy further enhanced the efficacy with complete remission of gp70-negative CT26 tumors and survival of all mice. Our data highlight the power of combining synergistic modes of action and warrants further exploration of the presented treatment schema.
Details
- Language :
- English
- ISSN :
- 21624011 and 2162402X
- Volume :
- 9
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- OncoImmunology
- Publication Type :
- Periodical
- Accession number :
- ejs54967791
- Full Text :
- https://doi.org/10.1080/2162402X.2020.1771925