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

Steffen Walter, Toni Weinschenk, Arnulf Stenzl, Romuald Zdrojowy, Anna Pluzanska, Cezary Szczylik, Michael Staehler, Wolfram Brugger, Pierre Yves Dietrich, Regina Mendrzyk, Norbert Hilf, Oliver Schoor, Jens Fritsche, Andrea Mahr, Dominik Maurer, Verona Vass, Claudia Trautwein, Peter Lewandrowski, Christian Flohr, Heike PohlaJanusz J. Stanczak, Vincenzo Bronte, Susanna Mandruzzato, Tilo Biedermann, Graham Pawelec, Evelyna Derhovanessian, Hisakazu Yamagishi, Tsuneharu Miki, Fumiya Hongo, Natsuki Takaha, Kosei Hirakawa, Hiroaki Tanaka, Stefan Stevanovic, Jürgen Frisch, Andrea Mayer-Mokler, Alexandra Kirner, Hans Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1254-1261
Number of pages8
JournalNature Medicine
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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