Background: Adjuvant therapies such as radiation therapy, chemotherapy, and immunotherapy are usually given after cancer surgery to improve the survival of cancer patients. However, despite advances in several adjuvant therapies, they are still limited in the prevention of recurrences. Methods: We evaluated the immunological effects of RNA-based adjuvants in a murine melanoma model. Single-stranded RNA (ssRNA) were constructed based on the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Populations of immune cells in bone marrow cells and lymph node cells following immunization with CrPVIRES-ssRNA were determined using flow cytometry. Activated cytokine levels were measured using ELISA and ELISpot. The tumor protection efficacy of CrPVIRES-ssRNA was analyzed based on any reduction in tumor size or weight, and overall survival. Results: CrPVIRES-ssRNA treatment stimulated antigen-presenting cells in the drain lymph nodes associated with activated antigen-specific dendritic cells. Next, we evaluated the expression of CD40, CD86, and XCR1, showing that immunization with CrPVIRES-ssRNA enhanced antigen presentation by CD8a+ conventional dendritic cell 1 (cDC1), as well as activated antigen-specific CD8 T cells. In addition, CrPVIRES-ssRNA treatment markedly increased the frequency of antigen-specific CD8 T cells and interferon-gamma (IFN-γ) producing cells, which promoted immune responses and reduced tumor burden in melanoma-bearing mice. Conclusions: This study provides evidence that the CrPVIRES-ssRNA adjuvant has potential for use in therapeutic cancer vaccines. Moreover, CrPVIRES-ssRNA possesses protective effects on various cancer cell models.
Bibliographical noteFunding Information:
J.-H.N. was supported by the Research Unit of Korea Center for Disease Control and Prevention grant (grant number 2020-ER5303-02), the National Research Foundation of Korea (NRF) grant (grant number NRF-2021M3E5E3080588), the Ministry of Food and Drug Safety grant (grant number 22213MFDS421) and partially supported by the Brain Korea 21 Plus Program, H.-J.P. is supported by the grant from the Ministry of Food and Drug Safety in 2022 (grant number 22203MFDS404).
© 2022, The Author(s).
- Adjuvant immunotherapy
- Antigen-presenting cells
- Murine melanoma model
- RNA vaccine