Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery

Abstract

Significance Tuberculosis (TB) is the second most lethal pathogen worldwide. Pulmonary granulomas are a hallmark of this disease. By discovering similarities between granulomas and solid cancerous tumors, we identified a novel therapeutic target for TB, the abnormal granuloma-associated vasculature that contributes to the abnormal granuloma microenvironment. We then asked if we could “normalize” granuloma vasculature by blocking VEGF signaling, an approach originally shown to enhance cancer treatment. Our results demonstrate that bevacizumab, a widely prescribed anti-VEGF antibody for cancer and eye diseases, is able to create more structurally and functionally normal granuloma vasculature and improve the delivery of a low-molecular-weight tracer. This effect suggests that vascular normalization in combination with anti-TB drugs has the potential to enhance treatment in patients with TB.