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Novel cancer immunotherapy agents with survival benefit: recent successes and next steps

Nature Reviews Cancer volume 11, pages 805–812 (2011)Cite this article

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Abstract

The US Food and Drug Administration (FDA) recently approved two novel immunotherapy agents, sipuleucel-T and ipilimumab, which showed a survival benefit for patients with metastatic prostate cancer and melanoma, respectively. The mechanisms by which these agents provideclinical benefit are not completely understood. However, knowledge of these mechanisms will be crucial for probing human immune responses and tumour biology in order to understand what distinguishes responders from non-responders. The following next steps are necessary: first, the development of immune-monitoring strategies for the identification of relevant biomarkers; second, the establishment of guidelines for the assessment of clinical end points; and third, the evaluation of combination therapy strategies to improve clinical benefit.

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Figure 1: Basic mechanisms of T cell stimulation and inhibition.
Figure 2: Current therapies that induce effector T cell functions.
Figure 3: Clinical trial concepts.

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Acknowledgements

The authors' research work was supported by the Howard Hughes Medical Institute (for J.P.A.), the Ludwig Center for Cancer Immunotherapy (for P.S., J.D.W. and J.P.A.), a Prostate Cancer Foundation Challenge Award in Immunology (to P.S. and J.P.A.). P.S. also acknowledges support from an M. D. Anderson Cancer Center Physician Scientist Award, a Doris Duke Charitable Foundation Clinical Scientist Development Award, a Clinical Investigator Award from the Cancer Research Institute, a Melanoma Research Alliance Young Investigator Award, an American Cancer Society Mentored Research Scholar Grant and a US Department of Defense Prostate Cancer Idea Development Award.

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Authors and Affiliations

  1. Padmanee Sharma is at the Departments of Genitourinary Medical Oncology and Immunology, University of Texas M. D. Anderson Cancer Center, Box 0018-7, 1515 Holcombe Boulevard, Houston, Texas 77030, USA,

    Padmanee Sharma

  2. and also at the Ludwig Center for Cancer Immunotherapy, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.,

    Padmanee Sharma

  3. Klaus Wagner is at the Division of Medicine, University of Texas M. D. Anderson Cancer Center, Box 0018-7, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.,

    Klaus Wagner

  4. Jedd D. Wolchok and James P. Allison are at the Ludwig Center for Cancer Immunotherapy, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.,

    Jedd D. Wolchok & James P. Allison

  5. Jedd D. Wolchok is also at the Division of Melanoma Medical Oncology, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.,

    Jedd D. Wolchok

  6. James P. Allison is also at the Departments of Immunology and the Howard Hughes Medical Institute, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.,

    James P. Allison

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  1. Padmanee Sharma
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Correspondence to Padmanee Sharma or James P. Allison.

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Competing interests

P.S., J.D.W. and J.P.A. have all served as paid consultants for Bristol-Myers Squibb (BMS). P.S. has also served as a paid consultant for Dendreon, Inc. J.P.A. is the inventor of anti-CTLA4 and has family members who own stock in BMS. K.W. is currently employed by Genentech.

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Sharma, P., Wagner, K., Wolchok, J. et al. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer 11, 805–812 (2011). https://doi.org/10.1038/nrc3153

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