We've recently demonstrated that patients with metastatic melanoma exist in a state of constant, chronic inflammation and are not immunologically intact as had been believed. Further analysis demonstrated that vascular endothelial growth factor (VEGF) may be playing a key role in this immune dysregulation. Thus the question became: could therapeutic inhibition of VEGF lead to immune normalization and could this improve clinical outcomes. Fortuitously, we recently completed two clinical trials in patients with metastatic melanoma in which we used similar chemotherapy agents for both trials, but only one also used a VEGF inhibitor (bevacizumab). Preliminary analysis of a few patient samples from each trial demonstrated that the addition of anti-VEGF therapy did indeed normalize systemic immunity which in turn appeared to correlate with better clinical outcomes. In the current application, we propose to fully test this hypothesis and analyze all of the available stored blood specimens from the two clinical trials and answer this question. If true, this would suggest that immune enhancing efforts following immune normalization with a VEGF inhibitor may significantly improve clinical outcomes in cancer patients. Augmentation of normalized immunity after initial therapy with a VEGF inhibitor may be more effective than augmentation of dysfunctional immunity if the same immune agent is used without prior anti-VEGF therapy. This might explain why immune augmenting therapy alone is so rarely successful and seems to only benefit patients with minimal tumor burden. If our studies are positive, we will proceed on to test this hypothesis in a clinical trial.
|Effective start/end date||1/1/10 → …|
- Melanoma Research Alliance
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