caa a22 4500 47712562X CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970101xx s 000 0 eng 10.1023/A:1012038930172 doi (NATIONALLICENCE)springer-10.1023/A:1012038930172 Tumor Vascular Endothelium: Barrier or Target in Tumor Directed Drug Delivery and Immunotherapy [Elektronische Daten] [Grietje Molema, Lou de Leij, Dirk Meijer] The therapy of solid tumors with conventional chemotherapeutics, drug delivery preparations and immuno-modulatory agents directed against the tumor cells is corrupted by a major barrier presented by the tumor vasculature. Permeability of the tumor blood vessels for transport of small molecules and macromolecular drug-carrier conjugates is only sufficient in the blood vessels at the tumor-host interface. Downregulation of the expression of adhesion molecules, required for the facilitation of immune cell recruitment, by the tumor vascular endothelium results in an escape of the tumor from host defence. New therapeutic approaches for the treatment of solid tumors are aimed at the tumor vasculature, either at the endothelial cells themselves or at basement membrane or tumor stroma components. Angiogenesis can be directly blocked with angiogenesis inhibitors, while angiogenesis related factors can serve as tumor vasculature specific epitopes for drug delivery strategies. Some glycoproteins expressed by tumor endothelial cells or present in the basement membrane and tumor stroma are also potential tumor selective targets. Therapeutic modalities that are suitable for site specific delivery are agents that increase tumor accumulation of (targeted) chemo/radiotherapeutics through increasing tumor vascular permeability. The observation that for tumor growth the blood supply is a limiting factor, led to the development of strategies to inhibit angiogenesis or block the tumor blood flow. Manipulation of the expression of endothelial cell adhesion molecules by selectively delivering modulatory agents at or in the tumor vascular endothelial cells may induce (bispecific antibody mediated) host defense activity directed against the tumor cells. Plenum Publishing Corporation, 1997 tumor vascular endothelium nationallicence targeting nationallicence drug delivery nationallicence immunotherapy nationallicence angiogenesis nationallicence Molema Grietje Dept. Clinical Immunology, University Hospital Groningen (AZG), Hanzeplein 1, 9713 GZ, Groningen, the Netherlands aut de Leij Lou Dept. Clinical Immunology, section Tumor Immunology, the Netherlands aut Meijer Dirk Dept. Clinical Immunology, section Tumor Immunology, the Netherlands aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 2-10 0724-8741 14:1<2 1997 14 11095 https://doi.org/10.1023/A:1012038930172 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012038930172 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Molema Grietje Dept. Clinical Immunology, University Hospital Groningen (AZG), Hanzeplein 1, 9713 GZ, Groningen, the Netherlands aut NATIONALLICENCE 700 1- de Leij Lou Dept. Clinical Immunology, section Tumor Immunology, the Netherlands aut NATIONALLICENCE 700 1- Meijer Dirk Dept. Clinical Immunology, section Tumor Immunology, the Netherlands aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 2-10 0724-8741 14:1<2 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer