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

作者：Walter, Steffen; Weinschenk, Toni; Stenzl, Arnulf; Zdrojowy, Romuald; Pluzanska, Anna; Szczylik, Cezary; Staehler, Michael; Brugger, Wolfram; Dietrich, Pierre-Yves; Mendrzyk, Regina; Hilf, Norbert; Schoor, Oliver; Fritsche, Jens; Mahr, Andrea; Maurer, Dominik; Vass, Verona; Trautwein, Claudia; Lewandrowski, Peter; Flohr, Christian; Pohla, Heike; Stanczak, Janusz J.; Bronte, Vincenzo; Mandruzzato, Susanna; Biedermann, Tilo; Pawelec, Graham; Derhovanessian, Evelyna; Yamagishi, Hisakazu

来源：Nature Medicine, 2012, 18(8): 1254-+.

DOI：10.1038/nm.2883

• REGULATORY T-CELLS
• COLONY-STIMULATING FACTOR
• MYELOID SUPPRESSOR-CELLS
• DENDRITIC CELLS
• TUMOR-ANTIGEN
• MELANOMA PATIENTS
• HIGH-FREQUENCIES
• PEPTIDE VACCINE
• CUTTING EDGE
• IDENTIFICATION

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.

• 出版日期2012-8
• 单位河北医科大学