Title |
Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial
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Published in |
OncoImmunology, March 2015
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DOI | 10.1080/2162402x.2014.1001217 |
Pubmed ID | |
Authors |
Friedrich H Schmitz-Winnenthal, Nicolas Hohmann, Andreas G Niethammer, Tobias Friedrich, Heinz Lubenau, Marco Springer, Klaus M Breiner, Gerd Mikus, Jürgen Weitz, Alexis Ulrich, Markus W Buechler, Frank Pianka, Ulla Klaiber, Markus Diener, Christine Leowardi, Simon Schimmack, Leila Sisic, Anne-Valerie Keller, Ruhan Koc, Christoph Springfeld, Philipp Knebel, Thomas Schmidt, Yingzi Ge, Mariana Bucur, Slava Stamova, Lilli Podola, Walter E Haefeli, Lars Grenacher, Philipp Beckhove |
Abstract |
VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 71 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 12 | 17% |
Student > Ph. D. Student | 11 | 15% |
Student > Master | 8 | 11% |
Student > Doctoral Student | 7 | 10% |
Unspecified | 6 | 8% |
Other | 12 | 17% |
Unknown | 15 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 19 | 27% |
Biochemistry, Genetics and Molecular Biology | 10 | 14% |
Unspecified | 6 | 8% |
Immunology and Microbiology | 4 | 6% |
Agricultural and Biological Sciences | 3 | 4% |
Other | 12 | 17% |
Unknown | 17 | 24% |