This news release is available in Japanese.
Patients with metastatic melanoma who have benefited from a new type of cancer immunotherapy don't appear to share the same tumor-produced antigens, according to a new report by Eliezer Van Allen and colleagues. If the molecular targets for the immunotherapy differ from patient to patient, as this study suggests, it may be difficult to predict which patients will respond to the treatment. The drug, called ipilimumab, is part of a relatively new class of cancer treatments called immune checkpoint inhibitors. The inhibitors help reactivate the immune system in tumors so that the body's natural defenses can detect and kill off cancer cells. Previous small studies have shown that the patients who do best with ipilimumab are those with tumors that contain many mutations, since these mutations produce a plethora of new antigen proteins that the immune system attacks as foreign invaders. In the biggest study to date, Van Allen and colleagues studied tumor tissue from over 100 patients with metastatic melanoma and confirmed that the patients with the most tumor "neoantigens" were also those most likely to respond positively to ipilimumab. However, only a very small percentage of these neoantigens were found in more than one patient who benefited from the drug.
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Article #15: "Genomic correlates of response to CTLA4 blockade in metastatic melanoma," by E.M. Van Allen; D. Miao; S.A. Shukla; C.J. Wu; L.A. Garraway at Dana-Farber Cancer Institute in Boston, MA; E.M. Van Allen; D. Miao; S.A. Shukla; S. Gabriel; C.J. Wu; L.A. Garraway at Broad Institute of MIT and Harvard in Cambridge, MA; B. Schilling; L. Zimmer; A. Sucker; U. Hillen; D. Schadendorf at University Hospital, University Duisberg-Essen in Essen, Germany; B. Schilling; L. Zimmer; A. Sucker; U. Hillen; D. Schadendorf at German Cancer Consortium in Heidelberg, Germany; C. Blank; M.H. Geukes Foppen at Netherlands Cancer Institute in Amsterdam, Netherlands; S.M. Goldinger; R. Dummer at University Hospital Zurich in Zurich, Switzerland; J. Utikal at German Cancer Research Center in Heidelberg, Germany; J. Utikal at University Hospital Mannheim in Mannheim, Germany; J.C. Hassel at University Hospital Heidelberg in Heidelberg, Germany; B. Weide at University Hospital Tübingen in Tübingen, Germany; K.C. Kaehler at University Hospital Kiel in Kiel, Germany; C. Loquai at University Hospital Mainz in Mainz, Germany; P. Mohr at Elbe-Kliniken in Buxtehede, Germany; R. Gutzmer at University Hospital Hannover in Hannover, Germany.
Journal
Science