Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 XXXX Model.

@entity32 @entity5 @entity19 @entity11 @entity463
UNASSIGNED: The addition of antiangiogenic therapy to the standard-of-care treatment regimen for recurring @entity463 has provided some clinical benefits while also delineating numerous caveats, prompting evaluation of the elicited alterations to the @entity5 microenvironment. Of critical importance, given the steadily increasing incorporation of immunotherapeutic approaches clinically, is an enhanced understanding of the interplay between angiogenic and immune response pathways within @entity5 . In the present study, the GL261 @entity11 @entity19 model was used to determine the effects of antiangiogenic treatment in an immune-competent host. Following weekly systemic administration of aflibercept, an inhibitor of vascular endothelial growth factor, @entity5 volume was assessed by magnetic resonance imaging and changes to the @entity5 microenvironment were determined. Treatment with aflibercept resulted in reduced @entity5 burden and increased survival compared with controls. Additionally, decreased vascular permeability and preservation of the integrity of tight junction proteins were observed. Treated @entity5 also displayed hallmarks of anti-angiogenic evasion, including marked upregulation of vascular endothelial growth factor expression and increased @entity5 invasiveness. Aflibercept was then administered in combination with a picornavirus-based antitumor vaccine and @entity5 progression was evaluated. This combination therapy significantly delayed @entity5 progression and extended survival beyond that observed for either therapy alone. As such, this work demonstrates the efficacy of combined antiangiogenic and immunotherapy approaches for treating established @entity11 and provides a foundation for further evaluation of the effects of antiangiogenic therapy in the context of endogenous or vaccine-induced @entity32 responses.
