Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in @entity1 with advanced XXXX : A randomized, placebo-controlled, phase 1 trial.

@entity1 @entity788 @entity137 @entity7 @entity5 @entity319 @entity536 @entity5746
UNASSIGNED: @entity319 is expressed on @entity5 vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied @entity5 vaccine based on live, @entity536 bacteria carrying an expression plasmid, encoding @entity319 . We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to @entity319 and anti-angiogenic effects in advanced @entity788 @entity1 in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, @entity788 @entity1 were enrolled. In five escalating dose groups, 30 @entity1 received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting @entity137 were observed. @entity5746 -specific humoral immune responses occurred in the two highest dose groups. @entity319 specific Teff, but not Treg responses were overall increased in vaccinated @entity1 . We furthermore observed a significant reduction of @entity5 perfusion after 38 d in vaccinated @entity1 together with increased levels of serum biomarkers indicative of anti-angiogenic activity, @entity7 , and collagen IV. Vaccine specific Teff responses significantly correlated with @entity5 perfusion and high levels of preexisting @entity319 -specific Teff while those showing no antiangiogenic activity had low levels of preexisting @entity319 specific Teff, showed a transient early increase of @entity319 -specific Treg and reduced levels of @entity319 -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.
