Alternative targeting strategies

While most tumor vasculature appears to be generated via the proliferation, migration, and differentiation of ‘mature’ endothelial cells lining blood vessels in nearby normal tissues, it has become evident in recent years that there also exists a small but significant population of endothelial precursor cells in the bone marrow and blood that have the capacity under appropriate conditions to home to sites of active angiogenesis where they may contribute to the formation of new vessels (Rafii, 2000; Rafii and Lyden, 2003; Reyes et al., 2002). Assuming such cells can be harvested in sufficient numbers or maintained and expanded in vitro, then the possibility exists that they could be genetically engineered ex vivo and used subsequently as vehicles to carry therapeutic genes to tumor sites. Indeed, this approach has already been explored and its potential efficacy confirmed in a number of preclinical studies (Davidoff et al., 2001; De Palma et al., 2003; Lyden et al., 2001). Technologies that permit the isolation and genetic manipulation of hemopoietic progenitor cells are already well established and it does not seem unreasonable to expect that similar approaches could perhaps be applied to endothelial cell precursors, facilitating rapid clinical development of the strategy. It is important to keep in mind, however, that the precise phenotype of endothelial precursor cells remains the subject of some debate and much needs to be discovered concerning the mechanisms that control their recruitment to, and expansion in, the tumor vasculature.

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  • Category: Cancer