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Title

Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival

Authors
Walter, Steffen
Weinschenk, Toni
Stenzl, Arnulf
Zdrojowy, Romuald
Pluzanska, Anna
Szczylik, Cezary
Staehler, Michael
Brugger, Wolfram
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Published in Nature Medicine. 2012, vol. 18, no. 8, p. 1254-61
Abstract IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02(+) subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)(+) regulatory T (T(reg)) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of T(reg) cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.
Keywords Antigens, Neoplasm/immunologyApolipoprotein A-I/bloodBiological MarkersCD8-Positive T-Lymphocytes/immunologyCancer Vaccines/therapeutic useCarcinoma, Renal Cell/blood/drug therapy/immunology/therapyChemokine CCL17/bloodCombined Modality TherapyCyclophosphamide/administration & dosage/pharmacology/therapeutic useFemaleGranulocyte-Macrophage Colony-Stimulating Factor/therapeutic useHLA-A2 Antigen/immunologyHumansImmunosuppressive Agents/administration & dosage/pharmacology/therapeutic useImmunotherapy, ActiveKaplan-Meier EstimateKidney Neoplasms/blood/drug therapy/immunology/therapyLymphocyte DepletionMaleMiddle AgedPredictive Value of TestsPrognosisT-Lymphocytes, Regulatory/drug effects/immunologyTreatment OutcomeVaccines, Subunit/therapeutic use
Identifiers
PMID: 22842478
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Research group Immunothérapie des cancers (42)
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WALTER, Steffen et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. In: Nature Medicine, 2012, vol. 18, n° 8, p. 1254-61. https://archive-ouverte.unige.ch/unige:43568

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Deposited on : 2014-12-16

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