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

BACKGROUND & AIMS: We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5 year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatme...

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Autores principales: Löffler, Markus W., Chandran, P. Anoop, Laske, Karoline, Schroeder, Christopher, Bonzheim, Irina, Walzer, Mathias, Hilke, Franz J., Trautwein, Nico, Kowalewski, Daniel J., Schuster, Heiko, Günder, Marc, Carcamo Yañez, Viviana A., Mohr, Christopher, Sturm, Marc, Nguyen, Huu-Phuc, Riess, Olaf, Bauer, Peter, Nahnsen, Sven, Nadalin, Silvio, Zieker, Derek, Glatzle, Jörg, Thiel, Karolin, Schneiderhan-Marra, Nicole, Clasen, Stephan, Bösmüller, Hans, Fend, Falko, Kohlbacher, Oliver, Gouttefangeas, Cécile, Stevanović, Stefan, Königsrainer, Alfred, Rammensee, Hans-Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756536/
https://www.ncbi.nlm.nih.gov/pubmed/27397612
http://dx.doi.org/10.1016/j.jhep.2016.06.027
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author Löffler, Markus W.
Chandran, P. Anoop
Laske, Karoline
Schroeder, Christopher
Bonzheim, Irina
Walzer, Mathias
Hilke, Franz J.
Trautwein, Nico
Kowalewski, Daniel J.
Schuster, Heiko
Günder, Marc
Carcamo Yañez, Viviana A.
Mohr, Christopher
Sturm, Marc
Nguyen, Huu-Phuc
Riess, Olaf
Bauer, Peter
Nahnsen, Sven
Nadalin, Silvio
Zieker, Derek
Glatzle, Jörg
Thiel, Karolin
Schneiderhan-Marra, Nicole
Clasen, Stephan
Bösmüller, Hans
Fend, Falko
Kohlbacher, Oliver
Gouttefangeas, Cécile
Stevanović, Stefan
Königsrainer, Alfred
Rammensee, Hans-Georg
author_facet Löffler, Markus W.
Chandran, P. Anoop
Laske, Karoline
Schroeder, Christopher
Bonzheim, Irina
Walzer, Mathias
Hilke, Franz J.
Trautwein, Nico
Kowalewski, Daniel J.
Schuster, Heiko
Günder, Marc
Carcamo Yañez, Viviana A.
Mohr, Christopher
Sturm, Marc
Nguyen, Huu-Phuc
Riess, Olaf
Bauer, Peter
Nahnsen, Sven
Nadalin, Silvio
Zieker, Derek
Glatzle, Jörg
Thiel, Karolin
Schneiderhan-Marra, Nicole
Clasen, Stephan
Bösmüller, Hans
Fend, Falko
Kohlbacher, Oliver
Gouttefangeas, Cécile
Stevanović, Stefan
Königsrainer, Alfred
Rammensee, Hans-Georg
author_sort Löffler, Markus W.
collection PubMed
description BACKGROUND & AIMS: We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5 year 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.
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spelling pubmed-57565362018-01-10 Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient Löffler, Markus W. Chandran, P. Anoop Laske, Karoline Schroeder, Christopher Bonzheim, Irina Walzer, Mathias Hilke, Franz J. Trautwein, Nico Kowalewski, Daniel J. Schuster, Heiko Günder, Marc Carcamo Yañez, Viviana A. Mohr, Christopher Sturm, Marc Nguyen, Huu-Phuc Riess, Olaf Bauer, Peter Nahnsen, Sven Nadalin, Silvio Zieker, Derek Glatzle, Jörg Thiel, Karolin Schneiderhan-Marra, Nicole Clasen, Stephan Bösmüller, Hans Fend, Falko Kohlbacher, Oliver Gouttefangeas, Cécile Stevanović, Stefan Königsrainer, Alfred Rammensee, Hans-Georg J Hepatol Article BACKGROUND & AIMS: We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5 year 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. Elsevier 2016-10 /pmc/articles/PMC5756536/ /pubmed/27397612 http://dx.doi.org/10.1016/j.jhep.2016.06.027 Text en © 2016 European Association for the Study of the Liver. Elsevier B.V. All rights reserved. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Löffler, Markus W.
Chandran, P. Anoop
Laske, Karoline
Schroeder, Christopher
Bonzheim, Irina
Walzer, Mathias
Hilke, Franz J.
Trautwein, Nico
Kowalewski, Daniel J.
Schuster, Heiko
Günder, Marc
Carcamo Yañez, Viviana A.
Mohr, Christopher
Sturm, Marc
Nguyen, Huu-Phuc
Riess, Olaf
Bauer, Peter
Nahnsen, Sven
Nadalin, Silvio
Zieker, Derek
Glatzle, Jörg
Thiel, Karolin
Schneiderhan-Marra, Nicole
Clasen, Stephan
Bösmüller, Hans
Fend, Falko
Kohlbacher, Oliver
Gouttefangeas, Cécile
Stevanović, Stefan
Königsrainer, Alfred
Rammensee, Hans-Georg
Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
title Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
title_full Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
title_fullStr Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
title_full_unstemmed Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
title_short Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
title_sort personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756536/
https://www.ncbi.nlm.nih.gov/pubmed/27397612
http://dx.doi.org/10.1016/j.jhep.2016.06.027
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