mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

Radiation Oncology

Table 3 Genes differentially regulated upon combination therapy in comparison to vaccinated mice

Pathway/function	Downregulated genes
Genes associated with tumor invasiveness	Adam18 (6.7), Adam9 (1.6), Tgfbi (1.7), Mmp12 (1.8), Mmp3 (2.0), Mmp10 (2.2), Slc7a2 (2.4)
Tumor associated factors	Ly6i (3.1), Lrrc15 (2.4), Mamdc2 (2.4), Tm2d2 (2.1), Gpr97 (2.3), Grem1 (2.5), Dok4 (2.4), Tacc1 (2.3), Inhba (2.0), Ifitm1 (2.4)
Pathway/function	Upregulated genes
Genes associated with tumor suppresion	Phlda1 (2.3), Cxcl14 (2.4), Cd209a (2.4), Timp1 (1.9), Sfrp4 (3.9), Sulf1 (1.8), Nr1d1 (1.8), Ogn (5.0), Scara3 (2.3), Dpt (5.0)

C57BL/6 mice (4 mice per group) were challenged subcutaneously on the right limb with 3 × 10⁵ syngenic E.G7-OVA tumor cells. Mice were treated with the radioimmunotherapy starting at day 13 (local radiation of 6 Gy applied in 3 equal doses on 3 consecutive days and three vaccination with OVA-encoded mRNA – 32 μg, 2x week). OVA-encoded mRNA vaccinated mice served as controls. After 7 days tumors were exercised, RNA was isolated and gene expression was analyzed. Differentially expressed genes were identified by statistical analysis with the p ≤ 0.05 and a fold change of at least 1.5. The exact fold change is presented in the brackets.

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