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PMID: 22842478 Published · ppublish English Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

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

Nature medicine ·Vol. 18 ·No. 8 ·2012-08-00 ·Pages 1254-61

Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R, Hilf N, Schoor O, Fritsche J, Mahr A, Maurer D, Vass V, Trautwein C, Lewandrowski P, Flohr C, Pohla H, Stanczak JJ, Bronte V, Mandruzzato S, Biedermann T, Pawelec G, Derhovanessian E, Yamagishi H, Miki T, Hongo F, Takaha N, Hirakawa K, Tanaka H, Stevanovic S, Frisch J, Mayer-Mokler A, Kirner A, Rammensee HG, Reinhardt C, Singh-Jasuja H

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.

MeSH Terms
Antigens, Neoplasm/immunology Apolipoprotein A-I/blood Biomarkers CD8-Positive T-Lymphocytes/immunology Cancer Vaccines/therapeutic use Carcinoma, Renal Cell/blood,drug therapy,immunology,therapy Chemokine CCL17/blood Combined Modality Therapy Cyclophosphamide/administration & dosage,pharmacology,therapeutic use Female Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use HLA-A2 Antigen/immunology Humans Immunosuppressive Agents/administration & dosage,pharmacology,therapeutic use Immunotherapy, Active Kaplan-Meier Estimate Kidney Neoplasms/blood,drug therapy,immunology,therapy Lymphocyte Depletion Male Middle Aged Predictive Value of Tests Prognosis T-Lymphocytes, Regulatory/drug effects,immunology Treatment Outcome Vaccines, Subunit/therapeutic use
Chemicals
APOA1 protein, human Antigens, Neoplasm Apolipoprotein A-I Biomarkers CCL17 protein, human Cancer Vaccines Chemokine CCL17 HLA-A*02 antigen HLA-A2 Antigen IMA901 vaccine Immunosuppressive Agents Vaccines, Subunit Granulocyte-Macrophage Colony-Stimulating Factor Cyclophosphamide
Authors & Affiliations
39 authors, click to expand affiliations / ORCID
Walter Steffen
Immatics Biotechnologies GmbH, Tübingen, Germany.
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
Miki Tsuneharu
Hongo Fumiya
Takaha Natsuki
Hirakawa Kosei
Tanaka Hiroaki
Stevanovic Stefan
Frisch Jürgen
Mayer-Mokler Andrea
Kirner Alexandra
Rammensee Hans-Georg
Reinhardt Carsten
Singh-Jasuja Harpreet
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.2883
Published
2012-08-00
Epub
2012-00-29
Pages
1254-61
Language
English
Region
United States
NLM ID
9502015
Subset
IM
External Links
PubMed source DOI: 10.1038/nm.2883 View journal details
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