Abstract
The recent success of cancer immunotherapies has highlighted the benefit of harnessing the immune system for cancer treatment. Vaccines have a long history of promoting immunity to pathogens and, consequently, vaccines targeting cancer neoantigens have been championed as a tool to direct and amplify immune responses against tumours while sparing healthy tissue. In recent years, extensive preclinical research and more than one hundred clinical trials have tested different strategies of neoantigen discovery and vaccine formulations. However, despite the enthusiasm for neoantigen vaccines, proof of unequivocal efficacy has remained beyond reach for the majority of clinical trials. In this Review, we focus on the key obstacles pertaining to vaccine design and tumour environment that remain to be overcome in order to unleash the true potential of neoantigen vaccines in cancer therapy.
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Acknowledgements
This work was supported by the Dutch Cancer Society (KWF grant 12837 to P.D.K.), the International Joint Usage/Research Center, the Institute of Medical Science, the University of Tokyo (projects 2019-K3010 and K22-3063 to P.D.K. and K.J.I.) and the National Institutes of Health (NIH grant R21 CA274064 to C.S.). The funders had no role in the study design, data collection and interpretation or the decision to submit the work for publication.
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P.D.K., K.J.I. and C.S. wrote the article. All authors contributed to researching the article and to the review and editing of the manuscript.
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Glossary
- Cross-presentation
-
MHC class I presentation of exogenous antigens sampled from the extracellular environment by professional antigen-presenting cells.
- Defective ribosomal products
-
(DRiPs). Nascent, immature proteins or polypeptides that are rapidly degraded after synthesis.
- Immunopeptidome
-
The entirety of all peptides presented by MHC molecules on the surface of cells.
- K3 type of CpG ODNs
-
(K3 CpG-ODNs). Nuclease-resistant oligonucleotides of the K type (also known as B class) that contain unmethylated cytosine–guanine dinucleotide (CpG) motifs and activate Toll-like receptor 9 (TLR9).
- Synthetic long peptides
-
(SLPs). Peptides, 15–50-amino acid long, that are chemically synthesized and used as antigens in peptide-based vaccine formulations.
- Trunk mutations
-
Cancer-associated mutations that occur early during transformation and are, consequently, shared by all progeny cancer cells.
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Katsikis, P.D., Ishii, K.J. & Schliehe, C. Challenges in developing personalized neoantigen cancer vaccines. Nat Rev Immunol 24, 213–227 (2024). https://doi.org/10.1038/s41577-023-00937-y
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DOI: https://doi.org/10.1038/s41577-023-00937-y
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