Personalized Peptide Vaccine-induced Immune Response Associated With Long-term Survival Of A Metastatic Cholangiocarcinoma Patient
JOURNAL OF HEPATOLOGY
Markus W. Löffler, P. Anoop Chandran, Karoline Laske, Christopher Schroeder,Irina Bonzheim, Mathias Walzer, Franz J. Hilke, Nico Trautwein, Daniel J. Kowalewski, Heiko Schuster, Marc Günder, Viviana A. Carcamo Yañez, Christopher Mohr, Marc Sturm, Huu-Phuc Nguyen, Olaf Riess, Peter Bauer, Sven Nahnsen, Silvio Nadalin, Derek Zieker, Jörg Glatzle, Karolin Thiel, Nicole Schneiderhan-Marra, Stephan Clasen, Hans Bösmüller, Falko Fend, Oliver Kohlbacher, Cécile Gouttefangeas, Stefan Stevanović, Alfred Königsrainer, Hans-Georg Rammensee
Journal of Hepatology
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.
Tumors were characterized by immunohistochemistry, next-generation sequencing and mass spectrometry of HLA ligands.
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.
This remarkable clinical course encourages formal clinical studies on adjuvant personalized peptide vaccination in cholangiocarcinoma.
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.