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Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | OncoImmunology | ||||
Verlag: | TAYLOR & FRANCIS INC | ||||
Ort der Veröffentlichung: | PHILADELPHIA | ||||
Band: | 7 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 4 | ||||
Seitenbereich: | e1303584 | ||||
Datum: | 2018 | ||||
Institutionen: | Medizin > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR 2; TUMOR-GROWTH; PEPTIDE VACCINATION; CLINICAL-TRIAL; BONE-MARROW; IMMUNOTHERAPY; ANGIOGENESIS; MICROENVIRONMENT; ADENOCARCINOMA; anti-angiogenesis; immune-oncology; human CD8(+) T cells; oral vaccination; pancreatic cancer; Salmonella typhi; VEGFR2 | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 47677 |
Zusammenfassung
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, ...
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Zusammenfassung
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 10(6) colony-forming units (CFU) or 10(7) 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 (IFN gamma) 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.
Metadaten zuletzt geändert: 28 Jul 2021 17:28