TY  - JOUR
A1  - Sonntag, Katja
A1  - Hashimoto, Hisayoshi
A1  - Eyrich, Matthias
A1  - Menzel, Moritz
A1  - Schubach, Max
A1  - Döcker, Dennis
A1  - Battke, Florian
A1  - Courage, Carolina
A1  - Lambertz, Helmut
A1  - Handgretinger, Rupert
A1  - Biskup, Saskia
A1  - Schilbach, Karin
T1  - 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
T2  - Journal of Translational Medicine
N2  - 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.
KW  - pancreatic carcinoma
KW  - therapeutic vaccines
KW  - neoepitope-derived peptides
KW  - T-cell responses
KW  - CDR3 sequences
Y1  - 2018
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23927
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-239276
VL  - 16
ER  -