Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report

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dc.contributor.author Sonntag, Katja
dc.contributor.author Hashimoto, Hisayoshi
dc.contributor.author Eyrich, Matthias
dc.contributor.author Menzel, Moritz
dc.contributor.author Schubach, Max
dc.contributor.author Döcker, Dennis
dc.contributor.author Battke, Florian
dc.contributor.author Courage, Carolina
dc.contributor.author Lambertz, Helmut
dc.contributor.author Handgretinger, Rupert
dc.contributor.author Biskup, Saskia
dc.contributor.author Schilbach, Karin
dc.date.accessioned 2018-02-11T04:38:26Z
dc.date.available 2018-02-11T04:38:26Z
dc.date.issued 2018-02-06
dc.identifier.citation Journal of Translational Medicine. 2018 Feb 06;16(1):23
dc.identifier.uri http://hdl.handle.net/10138/232273
dc.description.abstract Abstract Background Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. Methods Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-γ+ T cell responses against vaccine peptides in peripheral blood after 12, 17 and 34 vaccinations by analyzing T-cell receptor (TCR) repertoire diversity and epitope-binding regions of peptide-reactive T-cell lines and clones. By restricting analysis to sorted IFN-γ-producing T cells we could assure epitope-specificity, functionality, and TH1 polarization. Results A peptide-specific T-cell response against three of the four vaccine peptides could be detected sequentially. Molecular TCR analysis revealed a broad vaccine-reactive TCR repertoire with clones of discernible specificity. Four identical or convergent TCR sequences could be identified at more than one time-point, indicating timely persistence of vaccine-reactive T cells. One dominant TCR expressing a dual TCRVα chain could be found in three T-cell clones. The observed T-cell responses possibly contributed to clinical outcome: The patient is alive 6 years after initial diagnosis and in complete remission for 4 years now. Conclusions Therapeutic vaccination with a neoantigen-derived four-peptide vaccine resulted in a diverse and long-lasting immune response against these targets which was associated with prolonged clinical remission. These data warrant confirmation in a larger proof-of concept clinical trial.
dc.publisher BioMed Central
dc.subject Pancreatic carcinoma
dc.subject Therapeutic vaccines
dc.subject Neoepitope-derived peptides
dc.subject T-cell responses
dc.subject CDR3 sequences
dc.title Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report
dc.date.updated 2018-02-11T04:38:26Z
dc.language.rfc3066 en
dc.rights.holder The Author(s)
dc.type.uri http://purl.org/eprint/entityType/ScholarlyWork
dc.type.uri http://purl.org/eprint/entityType/Expression
dc.type.uri http://purl.org/eprint/type/JournalArticle

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