Immunotherapeutic Targeting of Tumor-Associated Blood Vessels

Pathological angiogenesis occurs during tumor progression and leads in the formation of an abnormal vasculature in the tumor microenvironment (TME). The tumor vasculature is disorganized, tortuous and leaky, resulting in high interstitial pressure and hypoxia in the TME, all of which are events that support tumor growth and survival. Given the sustaining role of the tumor vasculature, it has become an increasingly attractive target for the development of anti-cancer therapies. Antibodies, tyrosine kinase inhibitors and cancer vaccines that target pro-angiogenic factors, angiogenesis-associated receptors or tumor blood vessel-associated antigens continue to be developed and tested for therapeutic efficacy. Preferred anti-angiogenic protocols include those that "normalize" the tumor-associated vasculature which reduce hypoxia and improve tumor blood perfusion, resulting in tumor cell apoptosis, decreased immunosuppression, and enhanced effector immune cell infiltration/tumoricidal action within the TME.