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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 1 - Protein Evolution (A. Lupas)     Display Documents



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ID: 733224.0, MPI für Entwicklungsbiologie / Abteilung 1 - Protein Evolution (A. Lupas)
Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
Authors:Loffler, M. W.; Chandran, P. A.; Laske, K.; Schroeder, C.; Bonzheim, I.; Walzer, M.; Hilke, F. J.; Trautwein, N.; Kowalewski, D. J.; Schuster, H.; Gunder, M.; Carcamo Yanez, V. A.; Mohr, C.; Sturm, M.; Nguyen, H. P.; Riess, O.; Bauer, P.; Nahnsen, S.; Nadalin, S.; Zieker, D.; Glatzle, J.; Thiel, K.; Schneiderhan-Marra, N.; Clasen, S.; Bosmuller, H.; Fend, F.; Kohlbacher, O.; Gouttefangeas, C.; Stevanovic, S.; Konigsrainer, A.; Rammensee, H. G.
Date of Publication (YYYY-MM-DD):2016-10
Title of Journal:J Hepatol
Volume:65
Issue / Number:4
Start Page:849
End Page:855
Review Status:Internal review
Audience:Not Specified
Abstract / Description:BACKGROUND & AIMS: We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatment options, aiming at the induction of anti-tumor T cells responses, we initiated a personalized multi-peptide vaccination, based on in-depth analysis of tumor antigens (immunopeptidome) and sequencing. METHODS: Tumors were characterized by immunohistochemistry, next-generation sequencing and mass spectrometry of HLA ligands. RESULTS: Although several tumor-specific neo-epitopes were predicted in silico, none could be validated by mass spectrometry. Instead, a personalized multi-peptide vaccine containing non-mutated tumor-associated epitopes was designed and applied. Immunomonitoring showed vaccine-induced T cell responses to three out of seven peptides administered. The pulmonary metastasis resected after start of vaccination showed strong immune cell infiltration and perforin positivity, in contrast to the previous lesions. The patient remains clinically healthy, without any radiologically detectable tumors since March 2013 and the vaccination is continued. CONCLUSIONS: This remarkable clinical course encourages formal clinical studies on adjuvant personalized peptide vaccination in cholangiocarcinoma. LAY SUMMARY: Metastatic cholangiocarcinomas, cancers that originate from the liver bile ducts, have very limited treatment options and a fatal prognosis. We describe a novel therapeutic approach in such a patient using a personalized multi-peptide vaccine. This vaccine, developed based on the characterization of the patient's tumor, evoked detectable anti-tumor immune responses, associating with long-term tumor-free survival.
Free Keywords:Anti-tumor T cell response; Cholangiocarcinoma; Hla; Immunopeptidome; Immunotherapy; Peptides; Primary liver cancer
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilung 1 - Proteinevolution (Andrei Lupas)
External Affiliations:University of Tubingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tubingen, Germany. University of Tubingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tubingen, Germany; Current address: Immatics Biotechnologies GmbH, Paul Ehrlich Str. 15, 72076 Tubingen, Germany. University Hospital Tubingen, Institute of Medical Genetics and Applied Genomics, Calwerstr. 7, 72076 Tubingen, Germany. University Hospital Tubingen, Institute of Pathology, Liebermeisterstr. 8, 72076 Tubingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tubingen, Germany. University of Tubingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tubingen, Germany; University of Tubingen, Center for Bioinformatics, Sand 14, 72076 Tubingen, Germany; University of Tubingen, Dept. of Computer Science, Sand 14, 72076 Tubingen, Germany. NMI Natural and Medical Sciences Institute at the University of Tubingen, Markwiesenstrasse 55, 72770 Reutlingen, Germany. University of Tubingen, Center for Bioinformatics, Sand 14, 72076 Tubingen, Germany; University of Tubingen, Dept. of Computer Science, Sand 14, 72076 Tubingen, Germany. University Hospital Tubingen, Institute of Medical Genetics and Applied Genomics, Calwerstr. 7, 72076 Tubingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tubingen, Germany. University of Tubingen, Center for Bioinformatics, Sand 14, 72076 Tubingen, Germany; University of Tubingen, Quantitative Biology Center (QBiC), Auf der Morgenstelle 10, 72076 Tubingen, Germany. University Hospital Tubingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tubingen, Germany. University Hospital Tubingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tubingen, Germany; Current address: Klinikum Konstanz, Luisenstr. 7, 78464 Konstanz, Germany. University Hospital Tubingen, Department of Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, 72076 Tubingen, Germany. University Hospital Tubingen, Institute of Pathology, Liebermeisterstr. 8, 72076 Tubingen, Germany. University of Tubingen, Center for Bioinformatics, Sand 14, 72076 Tubingen, Germany; University of Tubingen, Dept. of Computer Science, Sand 14, 72076 Tubingen, Germany; University of Tubingen, Quantitative Biology Center (QBiC), Auf der Morgenstelle 10, 72076 Tubingen, Germany; Max Planck Institute for Developmental Biology, Spemannstr. 35, 72076 Tubingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tubingen, Germany. University of Tubingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tubingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tubingen, Germany. University Hospital Tubingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tubingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tubingen, Germany.
Identifiers:ISSN:1600-0641 (Electronic) 0168-8278 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/27397612 [ID No:2]
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