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Supporting data for "Bacterial and neoantigen strategies for developing cancer vaccines"
Tumors that have metastasized to other organs are the leading cause of mortality in cancer sufferers. Hindering invasive and migratory capabilities of tumor cells can offer new approaches to treat patients with malignant cancer. In our previous study, engineered Salmonella Typhimurium strains were shown to potently inhibit the metastasis of multiple mouse tumors. Here, we demonstrate that sera from Salmonella -treated mice impairs the migration ability of breast cancer cell line 4T1 in vitro. Our findings indicate that the PI3K-AKT pathway is involved in this inhibitory function. Further results show that 4T1 cells cocultured with Salmonella-treated mice serum down-regulate vimentin and N-cadherin expression. Likewise, the Salmonella-treated mice sera also showed similar inhibition of migration of human breast cancer cells, including MDA-MB-231, 1937 and BT459 cells.
In this study, efforts are also made to develop a rational design platform for neoantigen-based cancer vaccine therapy and evaluate the antitumor immunological effect of peptide-based prototype vaccines in a mouse bladder tumor model. By using our platform, we discover newly generated tumor-specific antigens by identifying somatic point mutations in MB49 bladder cancer cell lines. The following T-cell immunogenicity test demonstrate that our prediction platform is capable of accurately identifying safe and effective neoantigens from exome and transcriptome data. Furthermore, our results show that these neoantigens from the T cell druggable "mutanome" can elicit significant protective immunity against bladder tumor growth in a subcutaneous model, as well as have a strong therapeutic efficacy in an orthotopic tumor model.
Taken as a whole, since cancer is a multifactorial illness, no individual therapy is totally efficient. Additional scientific and clinical studies are expected to combine the greatest strengths of bacterial therapy and neoantigen-based vaccine, as well as other therapies together, as a tremendous weapon in the battle against cancer and metastases.