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J Hepatol. 2016 Oct;65(4):849-855. doi: 10.1016/j.jhep.2016.06.027. Epub 2016 Jul 7.

Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient.

Author information

1
University Hospital Tübingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; University of Tübingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Germany. Electronic address: markus.loeffler@med.uni-tuebingen.de.
2
University of Tübingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
3
University of Tübingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tübingen, Germany; Current address: Immatics Biotechnologies GmbH, Paul Ehrlich Str. 15, 72076 Tübingen, Germany.
4
University Hospital Tübingen, Institute of Medical Genetics and Applied Genomics, Calwerstr. 7, 72076 Tübingen, Germany.
5
University Hospital Tübingen, Institute of Pathology, Liebermeisterstr. 8, 72076 Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Germany.
6
University of Tübingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tübingen, Germany; University of Tübingen, Center for Bioinformatics, Sand 14, 72076 Tübingen, Germany; University of Tübingen, Dept. of Computer Science, Sand 14, 72076 Tübingen, Germany.
7
NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse 55, 72770 Reutlingen, Germany.
8
University of Tübingen, Center for Bioinformatics, Sand 14, 72076 Tübingen, Germany; University of Tübingen, Dept. of Computer Science, Sand 14, 72076 Tübingen, Germany.
9
University Hospital Tübingen, Institute of Medical Genetics and Applied Genomics, Calwerstr. 7, 72076 Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Germany.
10
University of Tübingen, Center for Bioinformatics, Sand 14, 72076 Tübingen, Germany; University of Tübingen, Quantitative Biology Center (QBiC), Auf der Morgenstelle 10, 72076 Tübingen, Germany.
11
University Hospital Tübingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany.
12
University Hospital Tübingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; Current address: Klinikum Konstanz, Luisenstr. 7, 78464 Konstanz, Germany.
13
University Hospital Tübingen, Department of Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany.
14
University Hospital Tübingen, Institute of Pathology, Liebermeisterstr. 8, 72076 Tübingen, Germany.
15
University of Tübingen, Center for Bioinformatics, Sand 14, 72076 Tübingen, Germany; University of Tübingen, Dept. of Computer Science, Sand 14, 72076 Tübingen, Germany; University of Tübingen, Quantitative Biology Center (QBiC), Auf der Morgenstelle 10, 72076 Tübingen, Germany; Max Planck Institute for Developmental Biology, Spemannstr. 35, 72076 Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Germany.
16
University of Tübingen, Interfaculty Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Germany.
17
University Hospital Tübingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Germany.

Abstract

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.

KEYWORDS:

Anti-tumor T cell response; Cholangiocarcinoma; HLA; Immunopeptidome; Immunotherapy; Peptides; Primary liver cancer

PMID:
27397612
PMCID:
PMC5756536
DOI:
10.1016/j.jhep.2016.06.027
[Indexed for MEDLINE]
Free PMC Article

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