Tumor Targeting with Transgenic Endothelial Cells

The formation of tumor supporting vessels can be accomplished by the sprouting of preexisting vessels, i.e. the proliferation of resident endothelial cells (angiogenesis) or by vasculogenesis, i.e. the de novo formation of vessels by circulating endothelial progenitor cells (EPC) presumably deriving from the bone marrow. Cytokines and chemokines released by tumors and inflamed tissue have been shown to recruit EPC and other progenitor cells from the circulation to home to sites of active vessel and tumor growth. Therefore, EPC-based therapies might be used to target specifically malignant tumors. Incorporated autologous cells thereby function as “Trojan horses” and deliver enzymes for activation of cytotoxic agents or release antiangiogenic proteins. However, the extent of EPC incorporation and the precise mechanisms by which EPC contribute to neovessels or migrate and invade tumor tissue are still under investigation. Furthermore, cells used for therapeutic purposes, regardless of their origin, have to be produced under Good Manufacturing Practice (GMP) conditions and should be at least homogenous and unequivocally characterized to minimize potential risks of malignant transformation in individuals after transplantation. Thus, this review will summarize the current knowledge on EPC, their ex-vivo propagation, genetic modification and homing to tumors in preclinical trials.