{"id":16916,"date":"2018-02-06T10:31:51","date_gmt":"2018-02-06T09:31:51","guid":{"rendered":"https:\/\/genomik-tuebingen.de\/?p=16916"},"modified":"2025-03-14T14:58:13","modified_gmt":"2025-03-14T13:58:13","slug":"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-vaccine","status":"publish","type":"post","link":"https:\/\/cegat.com\/de\/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-vaccine\/","title":{"rendered":"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."},"content":{"rendered":"

Sonntag K1<\/sup>, Hashimoto H1<\/sup>, Eyrich M2<\/sup>, Menzel M3<\/sup>, Schubach M4<\/sup>, D\u00f6cker D3<\/sup>, Battke F3<\/sup>, Courage C5<\/sup>, Lambertz H6<\/sup>, Handgretinger R1<\/sup>, Biskup S3<\/sup>, Schilbach K7,<\/sup>8<\/sup>.<\/p>\n<\/div><\/div><\/div><\/div><\/div>

Abstract<\/h2><\/div><\/div><\/div>

Background:<\/p>\n

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.<\/p>\n

Methods:<\/p>\n

Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-\u03b3+ 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-\u03b3-producing T cells we could assure epitope-specificity, functionality, and TH1 polarization.<\/p>\n

Results:<\/p>\n

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 TCRV\u03b1 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.<\/p>\n

Conclusions:<\/p>\n

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.<\/p>\n

Keywords:<\/p>\n

CDR3 sequences; Neoepitope-derived peptides; Pancreatic carcinoma; T-cell responses; Therapeutic vaccines<\/p>\n<\/div><\/div><\/div><\/div><\/div>