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Therapeutic vaccines for cancer: an overview of clinical trials

Key Points

  • Development of vaccines for the treatment of cancer has posed many challenges, but results from some recent studies have confirmed the potential for clinical benefit

  • Progress has been driven by advances in our understanding of cancer immunology and, in particular, the nature and dynamics of the tumour microenvironment

  • Many clinical trials may have failed to adequately account for how vaccines differ from other cancer therapies, and for immunosuppressive mechanisms that operate in the tumour microenvironment

  • Predictive biomarkers that can identify subpopulations of patients most likely to benefit from active immunotherapy are needed

  • Evidence from clinical trials suggest that clinical benefit might be greatest in patients with less advanced-stage malignancies

  • Future strategies should include steps to modify the tumour microenvironment to optimize tumour-specific immune responses

Abstract

The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.

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Figure 1
Figure 2: Steps in the development of a cellular immune response against tumour-associated antigen.
Figure 3: Roadmap to the development of predictive biomarkers for active immunotherapy.

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All authors researched the data for the article and provided substantial contributions to discussions of its content, wrote sections of the article, and reviewed and approved the final draft of the full manuscript.

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Correspondence to Håkan Mellstedt.

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I.F. has received a research grant from Merck KGaA. Views and opinions described do not necessarily reflect those of Merck KGaA. I.M. has provided consultancy to and received honoraria and research funding from Bristol-Myers Squibb. G.G. is employed by Ultimovacs AS and has stocks in Ultimovacs AS and Targovax AS and he has provided consultancy to and received honoraria from KAEL-GemVax and Lytix AS. C.H. is an employee and has stocks in BioNTech and GANYMED Pharmaceuticals, has provided consultancy to Apceth, Bayer, Baxter, BioNTech, GANYMED, immatics, Merck KGaA, SuppreMol and TRON, and received honoraria from the CCR (UK), Karolinska University, Stockholm (Sweden), Kurume Cluster (Japan), and Swiss National Science Foundation. G.P. has provided consultancy to CureVac and received honoraria from Recombio. S.S. and N.T. have provided consultancy and received honoraria from Merck KGaA and KAELGemVax, and has stocks in Kancera AB. H.M. has received honoraria and research funding from Merck KGaA. W.G., J.W. and C.Z. declare no competing interests.

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Active immunotherapies in phase II development (DOCX 49 kb)

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Melero, I., Gaudernack, G., Gerritsen, W. et al. Therapeutic vaccines for cancer: an overview of clinical trials. Nat Rev Clin Oncol 11, 509–524 (2014). https://doi.org/10.1038/nrclinonc.2014.111

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