Authors
Vandana Krishna, Venkata Vamsi Krishna Venuganti
Published in
European journal of pharmacology. Pages 179424. Oct 12, 2026. Epub Oct 12, 2026.
Abstract
Effective cancer immunotherapy requires an understanding of the tumor microenvironment (TME) to overcome immune suppression and provide a durable anti-tumor response. Here, we present preclinical evaluation of survivin antigen-encoded mRNA lipid nanoparticles (mRNA-LNPs) in a murine oral cancer model. In vivo anti-tumor efficacy studies in early-stage tumors (induced by MOC1 cells, tumor volume ∼100 mm3) showed complete tumor elimination within 7-10 days after survivin mRNA-LNPs administration. The mechanistic studies performed to analyze immune cell (including dendritic cells and T cells) activation using flow cytometry and complementary cytokine profiling by ELISA revealed immune reprogramming. Survivin mRNA-LNP administration showed a broad, multi-compartmental T-cell immune response compared with control group. The treatment group showed significantly greater CD4+ and CD8+ T cell expansion in lymph nodes by day 3 (p<0.0001) and robust infiltration into the TME by day 14 (p<0.001) compared with control group. The survivin mRNA-LNPs promoted T cell activation (CD69+, CD28+) and increased cytotoxic CD8+Granzyme B+ T cells in the TME (p<0.001). The survivin mRNA-LNPs group showed controlled Treg levels in the TME providing a favorable effector to Treg ratio critical for superior anti-tumor efficacy. Furthermore, tumor rechallenge study showed formation of immunological memory against oral cancer cells. In conclusion, the present study provides a mechanistic understanding of survivin mRNA-LNP-mediated immune modulation in oral cancer immunotherapy.
PMID:
42863555
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.
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