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  • Review Article
  • Published:

Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer

Key Points

  • Among the several approaches to cancer immunotherapy, cancer vaccines and monoclonal antibodies that block immune checkpoints are the most advanced clinically

  • Cancer vaccines, in which tumour antigen(s) are co-administered along with an adjuvant, generally do not produce objective tumour shrinkage

  • Monoclonal antibodies blocking immune checkpoints, such as CTLA-4 and PD-1, can mediate measurable tumour shrinkage (objective responses) in several cancer types, including lung cancer, kidney cancer and melanoma

  • Combination immunotherapy, which can involve a cancer vaccine administered with an immune checkpoint blocking antibody or the co-administration of two checkpoint blocking antibodies, might be important for maximizing clinical benefit

Abstract

Previously, clinical approaches to using the immune system against cancer focused on vaccines that intended to specifically initiate or amplify a host response against evolving tumours. Although vaccine approaches have had some clinical success, most cancer vaccines fail to induce objective tumour shrinkage in patients. More-recent approaches have centred on a series of molecules known as immune checkpoints—whose natural function is to restrain or dampen a potentially over-exuberant response. Blocking immune checkpoint molecules with monoclonal antibodies has emerged as a viable clinical strategy that mediates tumour shrinkage in several cancer types. In addition to being part of the current treatment armamentarium for metastatic melanoma, immune checkpoint blockade is currently undergoing phase III testing in several cancer types.

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Figure 1: Mechanism of action of cancer vaccines.
Figure 2: Immune checkpoint blockade.

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Acknowledgements

C. G. Drake is a Damon Runyon-Lilly Clinical Investigator and is supported by National Institutes of Health R01 CA127153, 1P50CA58236-15, the Patrick C. Walsh Fund, the One-in-Six Foundation, the Koch Foundation and the Prostate Cancer Foundation. E. J. Lipson is supported by the Melanoma Research Alliance and the John P. Hussman Foundation. J. R. Brahmer is supported by the Stand Up to Cancer Foundation.

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All authors researched the data for the article and co-wrote the article. C. G. Drake edited the manuscript prior to submission, and all three authors reviewed and edited the article before submission and after peer review.

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Correspondence to Charles G. Drake.

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C. G. Drake has served as a paid consultant to BMS, CoStim Pharmaceuticals, Dendreon, and Pfizer Inc. J. R. Brahmer has served as an unpaid advisory board member to BMS and a paid consultant for Merck. E. J. Lipson declares no competing interests.

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Drake, C., Lipson, E. & Brahmer, J. Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. Nat Rev Clin Oncol 11, 24–37 (2014). https://doi.org/10.1038/nrclinonc.2013.208

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