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

  • Front Immunol. 2022 Nov 9:13:1007285. doi: 10.3389/fimmu.2022.1007285.
Thi-Anh-Thuy Tran  1  2 ,  Young-Hee Kim  1 ,  Ga-Eun Kim  3 ,  Shin Jung  1  4 ,  In-Young Kim  1  4 ,  Kyung-Sub Moon  1  4 ,  Young-Jin Kim  1  4 ,  Tae-Kyu Lee  1  4 ,  Hyosuk Yun  5 ,  Je-Jung Lee  6  7 ,  Hyun-Ju Lee  6 ,  Chul Won Lee  5 ,  Tae-Young Jung  1  2  4
Affiliations
  • 1. Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
  • 2. Biomedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School, Hwasun, South Korea.
  • 3. Chonnam National University Medical School, Chonnam National University, Hwasun, South Korea.
  • 4. Department of Neurosurgery, Chonnam National University Medical School, and Hwasun Hospital, Hwasun, South Korea.
  • 5. Department of Chemistry, Chonnam National University, Gwangju, South Korea.
  • 6. Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
  • 7. Department of Internal Medicine, Chonnam National University Medical School, and Hwasun Hospital, Hwasun, South Korea.
PMID: 36439089 DOI: 10.3389/fimmu.2022.1007285
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.

Keywords
BIRC5; EphA2; anti-PD1; lenalidomide; long multi-epitope peptide.
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