Schmitz-Winnenthal, Friedrich H. and Hohmann, Nicolas and Schmidt, Thomas and Podola, Lilli and Friedrich, Tobias and Lubenau, Heinz and Springer, Marco and Wieckowski, Sebastien and Breiner, Klaus M. and Mikus, Gerd and Buechler, Markus W. and Keller, Anne-Valerie and Koc, Ruhan and Springfeld, Christoph and Knebel, Phillip and Bucur, Mariana and Grenacher, Lars and Haefeli, Walter E. and Beckhove, Philipp (2018) 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. ONCOIMMUNOLOGY, 7 (4): e1303584. ISSN 2162-402X,
Full text not available from this repository. (Request a copy)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 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.
| Item Type: | Article |
|---|---|
| Uncontrolled 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 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 11:42 |
| Last Modified: | 20 Mar 2020 11:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15407 |
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