Therapeutic cancer vaccines are an attractive approach for treating malignant tumours, and successful tumour eradication depends primarily on controlling tumour immunosuppression status as well as heterogeneity of tumour cells driven by epigenetic alterations.
Peptide-loaded dendritic cell (DC) prime and non-infectious peptide booster heterologous immunisations were assessed for the immunogenicity of polo-like kinase-1 (PLK1)-derived peptides. Heterologous vaccination regimen targeting multiple shared tumour antigens simultaneously with PD-L1 blockade was assessed against murine myeloid leukaemia.
A synthetic PLK1122 (DSDFVFVVL)-based heterologous vaccination generated large numbers of long-lasting antigen-specific CD8 T-cells eliciting therapeutic effects against various established tumours. The therapeutic efficacy of single antigen-targeting PLK1122-based vaccine with sufficient endurance of PD-L1 blockade toward C1498 leukaemia relied on the heterogeneous clonal levels of MHC-I and PD-L1 expression. A novel multi-peptide-based vaccination targeting PLK1 and survivin simultaneously along with PD1 blockade led to complete tumour eradication and long-term survival in mice with clonally heterologous C1498 myeloid leukaemia.
Our findings suggest that PLK1 could be an attractive immunotherapeutic target antigen for cancer immunotherapy, and that similar strategies would be applicable for the optimisation of cancer vaccines for the treatment of numerous viral diseases and malignant tumours.
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Ethics approval and consent to participate
All experiments were performed in accordance with relevant guidelines and regulations of Central Research Ethics Committee of the Catholic University of Korea. Animal experiments were approved by and performed in compliance with the guidelines and regulations by Institutional Animal Care and Use Committee (IACUC, protocol #CUMS-2019-0169-03) of the Catholic University of Korea. All participants consented to partake in the study. This study was performed in accordance with the Declaration of Helsinki. All cell lines used in the experiment were purchased from the American Type Culture Collection (ATCC).
Summarised primary research data are presented in the paper. No publicly available dataset has been generated as part of this work.
The authors declare no competing interests.
This research was supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C1748).
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Shin, A., Lee, S., Choi, H. et al. An effective peptide vaccine strategy circumventing clonal MHC heterogeneity of murine myeloid leukaemia. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-0955-y