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Dendritic Cell-Based Cancer Vaccines

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Cancer Immunotherapy Meets Oncology

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Abstract

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) of our immune system. Their main function is to acquire and process antigen material and migrate to the lymphoid tissues where they present it on their surface in order to control the activation of the specific immunity. In particular the adaptive immune response, mediated by B and T cells, proved important in eradicating a tumour. This boosted the development of DC-based cancer vaccines currently studied worldwide. So far, most clinical trials have vaccinated patients with ex vivo-generated monocyte-derived DCs (moDCs), matured in the presence of cytokines and loaded with tumour antigen via peptides, protein- or RNA-encoding tumour antigens or tumour lysates.

DC-based immunotherapy has proven to be feasible, safe, and able to induce cellular and humoral responses and demonstrated clinical efficacy in a number of patients. The results are even better if the DCs have been appropriately matured. However, only in a subset of patients, these encouraging results can be seen. Although the evidence on clinical responses is still limited, induced responses frequently result in long-term clinical effectiveness. To further improve DC vaccination in cancer patients, a number of variables are already being applied in clinical trials, including DC maturation via Toll-like receptors, and mRNA transfection to load antigen and especially the use of naturally occurring DC subsets instead of moDCs is promising.

The novel immune checkpoint inhibitors, such as the anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) monoclonal antibodies, expanded the immunotherapeutic repertoire for immunogenic tumours. This has opened the way for combination immunotherapy trials in order to overcome tumour escape mechanisms. As DC vaccines virtually have no side effects, they can be used much earlier in adjuvant settings. The full potential of DC-based cancer vaccines has not yet been fully exploited. Its place in cancer immunotherapy will be determined in the upcoming years.

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Authors and Affiliations

  1. Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 26, Nijmegen, GA 6525, The Netherlands

    H. Westdorp, K. F. Bol, M. Coşkuntürk, G. Schreibelt, I. J. M. de Vries & C. G. Figdor

  2. Department of Medical Oncology, Radboud University Medical Centre, Geert Grooteplein 8, 9101, Nijmegen, HB 6500, The Netherlands

    H. Westdorp, K. F. Bol & M. Coşkuntürk

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  1. H. Westdorp
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  2. K. F. Bol
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  3. M. Coşkuntürk
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  4. G. Schreibelt
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  5. I. J. M. de Vries
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  6. C. G. Figdor
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Correspondence to C. G. Figdor .

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Editors and Affiliations

  1. Immunotherapy Development Center (IDC), TRON-Translational Oncology University Medical Center, Johannes Gutenberg University, Mainz, Germany

    Cedrik Michael Britten

  2. Department of Immunotherapy Development Center, TRON-Translational Oncology University Medical Center, Johannes Gutenberg-University, Mainz, Germany

    Sebastian Kreiter

  3. Department of Immunotherapy Development Center, TRON-Translational Oncology University Medical Center, Johannes Gutenberg University, Mainz, Germany

    Mustafa Diken

  4. Department of Immunology, University of Tübingen, Tübingen, Germany

    Hans-Georg Rammensee

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Westdorp, H., Bol, K.F., Coşkuntürk, M., Schreibelt, G., de Vries, I.J.M., Figdor, C.G. (2014). Dendritic Cell-Based Cancer Vaccines. In: Britten, C., Kreiter, S., Diken, M., Rammensee, HG. (eds) Cancer Immunotherapy Meets Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-05104-8_8

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