Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens

Matthew M. Gubin, Xiuli Zhang, Heiko Schuster, Etienne Caron, Jeffrey P. Ward, Takuro Noguchi, Yulia Ivanova, Jasreet Hundal, Cora D. Arthur, Willem-Jan Krebber, Gwenn E. Mulder, Mireille Toebes, Matthew D. Vesely, Samuel S. K. Lam, Alan J. Korman, James P. Allison, Gordon J. Freeman, Arlene H. Sharpe, Erika L. Pearce, Ton N. Schumacher, Ruedi Aebersold, Hans-Georg Rammensee, Cornelis J. M. Melief, Elaine R. Mardis, William E. Gillanders, Maxim N. Artyomov and Robert D. Schreiber ()
Additional contact information
Matthew M. Gubin: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Xiuli Zhang: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Heiko Schuster: Institute of Cell Biology, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Partner Site Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
Etienne Caron: Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland
Jeffrey P. Ward: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Takuro Noguchi: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Yulia Ivanova: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Jasreet Hundal: The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
Cora D. Arthur: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Willem-Jan Krebber: ISA Therapeutics B.V., 2333 CH Leiden, The Netherlands
Gwenn E. Mulder: ISA Therapeutics B.V., 2333 CH Leiden, The Netherlands
Mireille Toebes: The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Matthew D. Vesely: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Samuel S. K. Lam: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Alan J. Korman: Bristol-Myers Squibb, 700 Bay Road
James P. Allison: The University of Texas MD Anderson Cancer Center
Gordon J. Freeman: Dana-Farber Cancer Institute, Harvard Medical School
Arlene H. Sharpe: Harvard Medical School
Erika L. Pearce: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Ton N. Schumacher: The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Ruedi Aebersold: Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland
Hans-Georg Rammensee: Institute of Cell Biology, and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Partner Site Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
Cornelis J. M. Melief: ISA Therapeutics B.V., 2333 CH Leiden, The Netherlands
Elaine R. Mardis: The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
William E. Gillanders: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Maxim N. Artyomov: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Robert D. Schreiber: Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA

Nature, 2014, vol. 515, issue 7528, 577-581

Abstract: A carcinogen-induced mouse tumour model is used here to show that mutant tumour-specific antigens are targets for CD8+ T-cell responses, mediating tumour regression after checkpoint blockade immunotherapy, and that these antigens can be used effectively in therapeutic vaccines; this advance potentially opens the door to personalized cancer vaccines.

Date: 2014
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DOI: 10.1038/nature13988

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