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

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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Correspondence to Padmanee Sharma or James P. Allison.

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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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