The feasibility to exploit fusion protein comprising Recoverin and HSP70 as cancer vaccine

Zhao, Yue (2022): The feasibility to exploit fusion protein comprising Recoverin and HSP70 as cancer vaccine. Dissertation, LMU München: Medizinische Fakultät

Abstract

Cancer now is the leading cause of mortality worldwide. Despite the advances in conventional cancer treatments, like surgery and chemotherapy, the survival of cancer patients remains unsatisfying. Currently, immunotherapy, as a novel therapeutic alternative, exhibits a great efficacy to struggle against tumors with high specificity. Among immunotherapies, cancer vaccine stands out due to its capability to train and bolster the immune system to eliminate malignant cells specifically. However, selecting a high immunogenetic and avid antigen is a critical issue in the development of cancer vaccines. Because of the existence of the blood-retina barrier, Recoverin, a Ca2+-binding protein located in the immunoprivileged zone — retina, exhibit a great capability to prime immune responses against it when being exposed to the immune system. Accumulating studies revealed that Recoverin was found to be aberrantly expressed in various types of cancer. Therefore, Recoverin possesses the potential to serve as an ideal antigen candidate for the exploitation of cancer vaccines. To enhance the immunogenicity of antigen, Recoverin HLA class I and II epitopes were fused to HSP70 protein, which was reported to function as a natural adjuvant. In this study, I examined the feasibility of the Recoverin fusion protein as cancer vaccines in vitro. Recoverin fusion protein was evidenced to induce the maturation and activation of DCs via upregulating the expression of CD83, CD80, and CD86. Moreover, I also found that the fusion protein stimulates the secretion of pro-inflammatory cytokines of DCs, like TNF-α and IL-6. Further investigation revealed that DCs pulsed with the fusion protein are capable to induce the activation of autologous CD8+ T lymphocytes. However, the immunosuppressive properties were also demonstrated in the fusion protein. DCs pulsed with the fusion protein exhibit an increased level of PD-L1 and are able to prompt the expansion of Treg cells. In conclusion, in vitro experiments demonstrated the ability of the fusion protein to stimulate immune responses, suggesting the possibility to apply the fusion protein as a cancer vaccine to struggle against Recoverin-expressing tumors.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 26. Juli 2022
• 1. Bericht­erstatter:in: Bazhin, Alexandr