We report a novel experi
mental i
mmunotherapeutic approach in a patient with
metastatic intrahepatic cholangiocarcino
ma. In the 5 year course of the disease, the initial tu
mor
mass, two local recurrences and a lung
metastasis were surgically re
moved. Lacking alternative treat
ment options, ai
ming at the induction of anti-tu
mor T cells responses, we initiated a personalized
multi-peptide vaccination, based on in-depth analysis of tu
mor antigens (i
mmunopeptido
me) 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 m>in silicom>, 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.