Journal Article

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

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

2012

Overview

In this issue, Walter et al. report the results of two clinical trials of a new therapeutic vaccine, IMA901, for the treatment of renal cell carcinoma (RCC). IMA901 consists of ten tumor-associated peptides identified as naturally presented T cell epitopes in RCC, and the authors show longer overall survival in subjects with immune responses to multiple vaccine peptides and identify serum and cellular biomarkers that may help predict overall survival in future studies of the vaccine. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/590 / 692/699/1585/1588/1351 / 692/699/67/1059/2325 / Antigens, Neoplasm - immunology / Apolipoprotein A-I - blood / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer vaccines / Cancer Vaccines - therapeutic use / Carcinoma, Renal Cell - blood / Carcinoma, Renal Cell - drug therapy / Carcinoma, Renal Cell - immunology / Carcinoma, Renal Cell - therapy / CD8-Positive T-Lymphocytes - immunology / Chemokine CCL17 - blood / Combined Modality Therapy / Cyclophosphamide / Cyclophosphamide - administration & dosage / Cyclophosphamide - pharmacology / Cyclophosphamide - therapeutic use / Disease control / Dosage and administration / Female / Gene expression / Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use / Health aspects / HLA-A2 Antigen - immunology / Humans / Immune response / Immune system / Immunosuppressive Agents - administration & dosage / Immunosuppressive Agents - pharmacology / Immunosuppressive Agents - therapeutic use / Immunotherapy, Active / Infectious Diseases / Kaplan-Meier Estimate / Kidney diseases / Kidney Neoplasms - blood / Kidney Neoplasms - drug therapy / Kidney Neoplasms - immunology / Kidney Neoplasms - therapy / Lymphocyte Depletion / Male / Medical prognosis / Metabolic Diseases / Middle Aged / Molecular Medicine / Neurosciences / Peptides / Polypeptides / Predictive Value of Tests / Prognosis / Survival / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology / Treatment Outcome / Vaccines / Vaccines, Subunit - therapeutic use