Lowe DB

Our work centers on the fascinating areas of tumor immunology and tumor angiogenesis. There is no question the power of the immune system in preventing or resolving cancer. Decades of pre-clinical work has now matured into viable anti-cancer therapeutics that are showing significant survival benefits in patients. One has to look only as far as gene... -engineered effector T cells or specific antibody-based therapies to appreciate the power of the immune system in halting tumorigenesis. However, we are also readily aware of the immuno-suppressive/-evasive nature of the solid tumor microenvironment (TME) that severely diminishes the effectiveness of antibodies and T cells. Established vascularized cancers tend to contain mature and immature vessels that confound blood flow rates within the lesion and promote localized areas of hypoxia and acidosis. The tumor-influenced endothelium also downregulates activating adhesion molecules that ultimately abrogate a T cells functional ability to traffick to and localize within the tumor bed. Yet, in cases where the effector T cell gains access to tumor cells, a layered fortress of immunosuppression awaits. TME-residing cells such as regulatory T cells and myeloid-derived suppressor cells elaborate soluble molecules that strip away a T cells ability to fight. Immune checkpoints have also received a great deal of attention and involve the TME engaging certain T cell molecules to downmodulate any forthcoming immune response. So, quite frankly, as the field moves forward to design and implement highly potent cancer immunotherapies, durable clinical responses will be unattainable unless decisive action is also taken against many of the TME-derived properties mentioned above. To this end, there are two interrelated areas in the lab that receive our focus: At the basic science level, we are performing studies to understand the mechanistic aspects and consequences of destroying components of tumor-derived blood vessels using the immune system. Additionally, we are attempting to ...Read More