The long multi-epitope peptide vaccine combined with adjuvants improved the therapeutic effects in a glioblastoma mouse model

Abstract

Emerging data have suggested that single short peptides have limited success as a cancer vaccine; however, extending the short peptides into longer multi-epitope peptides overcame the immune tolerance and induced an immune response. Moreover, the combination of adjuvants such as lenalidomide and anti-programmed cell death protein 1 (PD1) with a peptide vaccine showed potential vaccine effects in previous studies. Therefore, the effects of a long multi-epitope peptide vaccine in combination with lenalidomide and anti-PD1 were analyzed in this study. Long multi-epitope peptides from two MHCI peptides (BIRC597-104 and EphA2682-689) and the pan-human leukocyte antigen-DR isotype (HLA-DR) binding epitope (PADRE) were synthesized. The therapeutic effects of long multi-epitope peptides in combination with lenalidomide and anti-PD1 were confirmed in the murine GL261 intracranial glioma model. Immune cells’ distribution and responses to the long multi-epitope peptides in combination with these adjuvants were also estimated in the spleens, lymph nodes, and tumor tissues. The difference between long multi-epitope peptides and a cocktail of multi-epitope peptides combined with lenalidomide and anti-PD1 was also clarified. As a result, long multi-epitope peptides combined with lenalidomide and anti-PD1 prolonged the survival of mice according to the suppression of tumor growth in an intracranial mouse model. While long multi-epitope peptides combined with these adjuvants enhanced the percentages of activated and memory effector CD8+ T cells, the increase in percentages of regulatory T cells (Tregs) was observed in a cocktail of multi-epitope peptides combined with lenalidomide and anti-PD1 group in the tumors. Long multi-epitope peptides combined with these adjuvants also enhanced the function of immune cells according to the enhanced pro-inflammatory cytokines and cytotoxicity against GL261 cells in ex vivo. In conclusion, long multi-epitope peptides composed of MHCI peptides, BIRC5 and EphA2, and the MHCII peptide, PADRE, in combination with lenalidomide and anti-PD1 has the potential to improve the therapeutic effects of a vaccine against GBM.

Distinct Specialized Center of Excellence, the Story of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital

“…Prof. Kyung-Sub Moon has performed MD/PhD cooperation projects from the National Research Foundation of Korea on the “discovery of new molecular targets for overcoming anti-cancer resistance in malignant glioma (2016–2019),” and “discovery of glioblastoma treatment resistance factors based on genome analysis and research on their suppression mechanisms (2020–2023).” Additionally, collaborative joint research with various research groups has progressed including “identification of the role of cancer-related fibroblasts in malignant brain tumors” and “anticancer effects of Lichen derivatives in animal models of malignant brain tumors” [ 15 16 17 ]. Prof. Tae-Young Jung conducted the National Research Foundation’s new research (2014–2017) and follow-up research (2017–2020) on the “optimization of branched multi-peptide vaccine function with immunotherapy for glioma” as the main research field and a regional university excellent scientist project (2020–2023) is being conducted on “the mechanism of enhancing the efficacy of an optimized peptide cancer vaccine by irradiation in glioma” [ 18 19 20 ]. In addition, Prof. Shin Jung conducted international collaborative research on medulloblastoma and ependymoma with the University of Toronto, and as a result, numerous joint studies were published [ 21 22 23 24 25 26 ].…”