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Verfasst von:Schmitz-Winnenthal, Friedrich Hubertus [VerfasserIn]   i
 Hohmann, Nicolas [VerfasserIn]   i
 Schmidt, Thomas [VerfasserIn]   i
 Podola, Lilli [VerfasserIn]   i
 Friedrich, Tobias [VerfasserIn]   i
 Lubenau, Heinz [VerfasserIn]   i
 Springer, Marco [VerfasserIn]   i
 Wieckowski, Sébastien [VerfasserIn]   i
 Breiner, Klaus M. [VerfasserIn]   i
 Mikus, Gerd [VerfasserIn]   i
 Büchler, Markus W. [VerfasserIn]   i
 Keller, Anne-Valérie [VerfasserIn]   i
 Koc, Ruhan [VerfasserIn]   i
 Springfeld, Christoph [VerfasserIn]   i
 Knebel, Phillip [VerfasserIn]   i
 Bucur, Mariana [VerfasserIn]   i
 Grenacher, Lars [VerfasserIn]   i
 Haefeli, Walter E. [VerfasserIn]   i
 Beckhove, Philipp [VerfasserIn]   i
Titel:A phase 1 trial extension to assess immunologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against VEGFR2, in patients with advanced pancreatic cancer
Verf.angabe:Friedrich H. Schmitz-Winnenthal, Nicolas Hohmann, Thomas Schmidt, Lilli Podola, Tobias Friedrich, Heinz Lubenau, Marco Springer, Sébastien Wieckowski, Klaus M. Breiner, Gerd Mikus, Markus W. Büchler, Anne-Valerie Keller, Ruhan Koc, Christoph Springfeld, Phillip Knebel, Mariana Bucur, Lars Grenacher, Walter E. Haefeli, and Philipp Beckhove
E-Jahr:2018
Jahr:16 Jan 2018
Umfang:13 S.
Fussnoten:Published online: 16 Jan 2018 ; Gesehen am 06.04.2020
Titel Quelle:Enthalten in: OncoImmunology
Ort Quelle:Abingdon : Taylor & Franics, 2012
Jahr Quelle:2018
Band/Heft Quelle:7 (2018,4) Artikel-Nummer e1303584, 13 Seiten
ISSN Quelle:2162-402X
Abstract:VXM01 is a first-in-kind orally applied tumor vaccine based on live attenuated Salmonella typhi carrying an expression plasmid encoding VEGFR2, an antigen expressed on tumor vasculature and a stable and accessible target for anti-angiogenic intervention. A recent randomized, placebo-controlled, phase I dose-escalation trial in advanced pancreatic cancer patients demonstrated safety, immunogenicity and transient, T-cell response-related anti-angiogenic activity of four priming vaccinations applied within one week. We here evaluated whether monthly boost vaccinations are safe and can sustain increased frequencies of vaccine-specific T cells.Patients with advanced pancreatic cancer were randomly assigned at a ratio of 2:1 to priming with VXM01 followed by up to six monthly boost vaccinations, or placebo treatment. Vaccinations were applied orally at two alternative doses of either 106 colony-forming units (CFU) or 107 CFU, and concomitant treatment with standard-of-care gemcitabine during the priming phase, and any treatment thereafter, was allowed in the study. Immunomonitoring involved interferon-gamma (IFNγ) ELIspot analysis with long overlapping peptides spanning the entire VEGFR2 sequence.A total of 26 patients were treated. Treatment-related adverse events preferentially associated with VXM01 were decreases in lymphocyte numbers in the blood, increased frequencies of neutrophils and diarrhea. Eight out of 16 patients who received at least one boosting vaccination responded with pronounced, i.e. at least 3-fold, increase in VEGFR2-specific T cell response over baseline levels. In the VXM01 vaccination group, VEGFR2-specific T cells peaked preferentially during the boosting phase with an average 4-fold increase over baseline levels.In conclusion, prime/boost vaccination with VXM01 was safe and immunogenic and increased vaccine specific T cell responses compared with placebo treatment.
DOI:doi:10.1080/2162402X.2017.1303584
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1080/2162402X.2017.1303584
 DOI: https://doi.org/10.1080/2162402X.2017.1303584
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:anti-angiogenesis
 human CD8+ T cells
 immune-oncology
 oral vaccination
 pancreatic cancer
 Salmonella typhi
 VEGFR2
K10plus-PPN:1694143821
Verknüpfungen:→ Zeitschrift

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