Abstract
Background: Cancer immunotherapy is widely used as a treatment for cancer that works by improving the immune system with fewer side effects than conventional methods. Neoantigen vaccines are one form of immunotherapy that use cancer-specific neoantigens that are extracted from cancer patients and are not recognized by normal cells in the immune system.Methods: In this study, mutant genes of 4T1 mouse breast cancer cells were identified by direct sequence analysis using tumor-specific MHC I (Major Histocompatibility Complex) or MHC II epitopes through in vivo experiments. Results: The neoantigen vaccine with mutant CD4+ or CD8+ T cell-reactive neoantigen peptides was shown to inhibit tumor growth, increase long-term survival, and induce the secretion of IFN-γ (Interferon gamma) in the cisplatin-treated mouse models. In particular, mutant CD4+ T cell neoantigen peptides induced full potential anti-tumor effects, whereas dual treatment with CD4+ (Cluster of differentiation 4) and CD8+ (Cluster of differentiation 8) T cell neoantigen peptides increased the suppression of tumor growth. Moreover, the combination of neoantigen vaccine with mutant CD4+ T cell neoantigen peptide and anti-PD-L1 (Programmed death-ligand 1) as an immune checkpoint inhibitor (ICI) has been shown to have synergistic therapeutic effects in cisplatin-treated mouse models. Conclusion: This study, therefore, proved that cancer cell-derived neoantigens have great potential to induce immunogenic responses and cancer treatment effects, along with synergistic efficiency when applied to various combinational therapies. Through the methods that were used in our experiments, we could contribute to the development of new adjuvants for evaluating efficacy, discovering unfound neoantigens, and investigating immune checkpoint blockade antibodies for non-clinical studies.
Nanoparticle delivery of immunostimulatory oligonucleotides enhances response to checkpoint inhibitor therapeutics
