Antitumour dendritic cell vaccination in a priming and boosting approach

Abstract

Mobilizing antitumour immunity through vaccination potentially constitutes a powerful anticancer strategy but has not yet provided robust clinical benefits in large patient populations. Although major hurdles still exist, we believe that currently available strategies for vaccines that target dendritic cells or use them to present antitumour antigens could be integrated into existing clinical practice using prime–boost approaches. In the priming phase, these approaches capitalize on either standard treatment modalities to trigger in situ vaccination and release tumour antigens or vaccination with dendritic cells loaded with tumour lysates or patient-specific neoantigens. In a second boost phase, personalized synthetic vaccines specifically boost T cells that were triggered during the priming phase. This immunotherapy approach has been enabled by the substantial recent improvements in dendritic cell vaccines. In this Perspective, we discuss these improvements, highlight how the prime–boost approach can be translated into clinical practice and provide solutions for various anticipated hurdles.

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Fig. 1: Mechanisms involved in tumour immunogenicity induced by standard treatment modalities.
Fig. 2: Key aspects involved in the design of whole tumour-based anticancer therapeutic vaccines.
Fig. 3: Potential sources of tumour neoantigens.
Fig. 4: A dendritic cell-based synthetic vaccine in a priming and boost approach.

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Acknowledgements

The authors thank K. Balint for assisting in collecting information in Table 1, P. Romero for critically reading the manuscript and G. Coukos for useful discussion.

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Harari, A., Graciotti, M., Bassani-Sternberg, M. et al. Antitumour dendritic cell vaccination in a priming and boosting approach. Nat Rev Drug Discov 19, 635–652 (2020). https://doi.org/10.1038/s41573-020-0074-8

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