Review Article | Published:

The future of cancer treatment: immunomodulation, CARs and combination immunotherapy

Nature Reviews Clinical Oncology volume 13, pages 273290 (2016) | Download Citation

  • A Corrigendum to this article was published on 26 April 2016

This article has been updated

Abstract

In the past decade, advances in the use of monoclonal antibodies (mAbs) and adoptive cellular therapy to treat cancer by modulating the immune response have led to unprecedented responses in patients with advanced-stage tumours that would otherwise have been fatal. To date, three immune-checkpoint-blocking mAbs have been approved in the USA for the treatment of patients with several types of cancer, and more patients will benefit from immunomodulatory mAb therapy in the months and years ahead. Concurrently, the adoptive transfer of genetically modified lymphocytes to treat patients with haematological malignancies has yielded dramatic results, and we anticipate that this approach will rapidly become the standard of care for an increasing number of patients. In this Review, we highlight the latest advances in immunotherapy and discuss the role that it will have in the future of cancer treatment, including settings for which testing combination strategies and 'armoured' CAR T cells are recommended.

Key points

  • Cancer immunotherapies have the potential to generate robust antitumour responses; this can be achieved through several methods, such as modulatory antibodies or adoptive cellular therapy

  • Since 2010, clinical trials using different immunotherapeutic approaches to treat patients with several tumour types have yielded unprecedented results

  • In contrast with therapies that act on the tumour itself, immunotherapy-dependent antitumour responses can be sustained after the treatment has finished

  • The optimal efficacy of immunotherapy will likely be achieved with designs that include combinations of different immunotherapeutic approaches, or immunotherapy combined with other cancer treatments

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Change history

  • 26 April 2016

    In the sentence "Results of a phase I trial113 demonstrated that an agonist mAb targeting CD40 given as monotherapy has antitumour activity in patients with melanoma or RCC", CD40 should have read OX40. This error has been corrected in the online HTML and PDF versions of the article.

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Acknowledgements

The authors would like to thank their funders. D.N.K. receives support through the American Association for Cancer Research Amgen fellowship in Clinical/Translational Cancer Research and the American Philosophical Society Daland Fellowship in Clinical Investigation. E.L.S. receives support from the Conquer Cancer Foundation of ASCO, Lymphoma Research Foundation, MSKCC Technology Development Fund, and the Multiple Myeloma Research Foundation. R.B.J. receives support from the Annual Terry Fox Run for Cancer Research (New York, NY) organized by the Canada Club of New York, Carson Family Charitable Trust, Emerald Foundation, the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center (Innovations in the structures, functions and targets of monoclonal antibody-based drugs for cancer), Kate's Team, National Institutes of Health Grants (R01CA138738-05, PO1CA059350, PO1CA190174-01), and the William Lawrence and Blanche Hughes Foundation. J.D.W. receives funding support from Bristol-Myers Squibb, Emerald Foundation, Genentech, the Ludwig Center for Cancer Immunotherapy, Medimmune, Merck Pharmaceuticals, Polynoma Pharmaceuticals and Swim Across America.

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Author notes

    • Danny N. Khalil
    •  & Eric L. Smith

    These authors contributed equally to this work.

Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

    • Danny N. Khalil
    • , Eric L. Smith
    • , Renier J. Brentjens
    •  & Jedd D. Wolchok

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Contributions

All authors researched data for article, contributed to discussion of the content, wrote the manuscript and reviewed/edited the article before submission.

Competing interests

D.N.K. and E.L.S. and declare no competing interests. R.J.B. is a co.founder, stockholder, and consultant for Juno Therapeutics Inc. J.D.W. is a consultant for Bristol Myers Squibb, Genentech, Medimmune, Merck Pharmaceuticals and Polynoma Pharmaceuticals.

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Correspondence to Jedd D. Wolchok.

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DOI

https://doi.org/10.1038/nrclinonc.2016.25

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