Bioimmunotherapeutic targets on angiogenetic blood vessels in solid malignangies

Physiological angiogenesis is a tightly regulated process that occurs mainly during reproduction, development and wound healing. Although angiogenesis is a continuous process, different consecutive steps can be identified, including: i) release of pro-angiogenetic factors; ii) release of proteolytic enzymes; iii) endothelial cell migration, morphogenesis and proliferation. Angiogenesis is also a hallmark of malignant diseases, and an inverse correlation between tumor vascularity and survival was demonstrated. Thus, strategies aimed at interfering with tumor blood supply by targeting tumor vasculature, presently represent promising new approaches for the treatment of solid malignancies. In fact, at least 30 angiogenetic inhibitors, utilized alone or in combination with other therapeutic agents, are currently being tested in clinical trials in humans. In this paper, we will review current knowledges on selected molecules expressed by endothelial cells and involved in distinct steps of the angiogenetic process, that represent potential targets for bioimmunotherapeutic approaches in human malignancies.