Trends in Cardiovascular Medicine
Volume 16, Issue 3 , Pages 80-88 , April 2006

Vascular Targeting: Recent Advances and Therapeutic Perspectives

  • Amin Hajitou
    • ,
  • Renata Pasqualini

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Renata Pasqualini and Wadih Arap, Departments of Genitourinary Medical Oncology and Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
    • ,
  • Wadih Arap

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Renata Pasqualini and Wadih Arap, Departments of Genitourinary Medical Oncology and Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

References 

  1. Adams GP. Improving the tumor specificity and retention of antibody-based molecules. In Vivo. 1998;12:11–21
  2. Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 1998;279:377–380
  3. Arap W, Kolonin M, Trepel M, et al. Steps toward mapping the human vasculature by phage display. Nat Med. 2002;8:121–127
  4. Arap MA, Lahdenranta J, Mintz PJ, et al. Cell surface expression of the stress response chaperone GRP78 enables tumor targeting by circulating ligands. Cancer Cell. 2004;6:275–284
  5. Barbas CF, Burton DR, Scott JK, et al. Phage Display: a Laboratory Manual. New York: Cold Spring Harbor Press; 2000;
  6. Barrow PA, Soothill JS. Bacteriophage therapy and prophylaxis: Rediscovery and renewed assessment of potential. Trends Microbiol. 1997;5:268–271
  7. Blagosklonny MV. Antiangigogenic therapy and tumor progression. Cancer Cell. 2004;5:13–17
  8. Boisvert WA, Black AS, Curtiss LK. ApoA1 reduces free cholesterol accumulation in atherosclerotic lesions of ApoE-deficient mice transplanted with ApoE-expressing macrophages. Arterioscler Thromb Vasc Biol. 1999;19:525–530
  9. Borsi L, Balza E, Bestagno M, et al. Selective targeting of tumoral vasculature: comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin. Int J Cancer. 2002;102:75–85
  10. Bosslet K, Straub R, Blumrich M, et al. Elucidation of the mechanism enabling tumor selective prodrug monotherapy. Cancer Res. 1998;58:1195–1201
  11. Bradley G, Juranka PF, Ling V. Mechanism of multidrug resistance. Biochim Biophys Acta. 1988;948:87–128
  12. Brekken RA, Thorpe PE. Vascular endothelial growth factor and vascular targeting of solid tumors. Anticancer Res. 2001;21:4221–4229
  13. Brekken RA, Li C, Kumar S. Strategies for vascular targeting in tumors. Int J Cancer. 2002;100:123–130
  14. Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994;264:569–571
  15. Brooks PC, Montgomery AM, Rosenfeld M, et al. Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994;79:1157–1164
  16. Buchegger F, Haskell CM, Schreyer M. Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice. J Exp Med. 1983;158:413–427
  17. Burg MA, Pasqualini R, Arap W. NG2 proteoglycan-binding peptides target tumor neovasculature. Cancer Res. 1999;59:2869–2874
  18. Burrows FJ, Thorpe PE. Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature. Proc Natl Acad Sci U S A. 1993;90:8996–9000
  19. Carnemolla B, Borsi L, Balza E, et al. Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix. Blood. 2002;99:1659–1665
  20. Chillon M, Bosch A, Zabner J, et al. Group D adenoviruses infect primary central nervous system cells more efficiently than those from subgroup C. J Virol. 1999;73:2537–2540
  21. Curnis F, Sacchi A, Borgna L, et al. Enhancement of tumor necrosis factor α antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol. 2000;18:1185–1190
  22. Curnis F, Gasparri A, Sacchi A, et al. Targeted delivery of IFN gamma to tumor vessels uncouples antitumor from counterregulatory mechanisms. Cancer Res. 2005;65:2906–2913
  23. Curtiss LK, Boisvert WA. Apolipoprotein E and atherosclerosis. Curr Opin Lipidol. 2000;11:243–251
  24. Cybulsky MI, Gimbrone JRMA. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991;251:788–791
  25. Demartis S, Tarli L, Borsi L, et al. Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin. Eur J Nucl Med. 2001;28:534–539
  26. Dickerson EB, Akhtar N, Steinberg H, et al. Enhancement of the antiangiogenic activity of interleukin-12 by peptide targeted delivery of the cytokine to αvβ3 integrin. Mol Cancer Res. 2004;2:663–673
  27. Dienst A, Grunow A, Unruh M, et al. Specific occlusion of murine and human tumor vasculature by VCAM-1-targeted recombinant fusion proteins. J Natl Cancer Inst. 2005;97:733–747
  28. Dong ZM, Chapman SM, Brown AA. The combined role of P- and E-selectins in atherosclerosis. J Clin Invest. 1998;102:145–152
  29. Ellerby HM, Arap W, Ellerby LM. Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med. 1999;5:1032–1038
  30. Fahr A, Muller K, Nahde T, et al. A new colloidal lipidic system for gene therapy. J Liposome Res. 2002;12:37–44
  31. Folli S, Pelegrin A, Chalandon Y, et al. Tumor-necrosis factor can enhance radio-antibody uptake in human colon carcinoma xenografts by increasing vascular permeability. Int J Cancer. 1993;53:829–836
  32. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–1186
  33. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31
  34. Folkman J. In:  DeVita VT,  Hellman S,  Rosenberg SA editor. Cancer: Principles and practice of oncology. Philadelphia: Lippincott; 1997;p. 3075–3085
  35. French BA, Mazur W, Ali NM, et al. Percutaneous transluminal in vivo gene transfer by recombinant adenovirus in normal porcine coronary arteries, atherosclerotic arteries, and two models of coronary restenosis. Circulation. 1994;90:2402–2413
  36. Fuster V. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation. 1994;90:2126–2146
  37. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res. 2002;90:251–262
  38. Giordano RJ, Cardo-Vila M, Lahdenranta J, et al. Biopanning and rapid analysis of selective interactive ligands. Nat Med. 2001;7:1249–1253
  39. Girod A, Ried M, Wobus C, et al. Genetic capsid modifications allow efficient re-targeting of adeno-associated virus type 2. Nat Med. 1999;5:1052–1056
  40. Grines C, Watkins M, Helmer G, et al. Angiogenic Gene Therapy (AGENT) trial in patients with stable angina pectoris. Circulation. 2002;105:1291–1297
  41. Halin C, Rondini S, Nilsson F, et al. Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature. Nat Biotechnol. 2002;20:264–269
  42. Hammes HP, Brownlee M, Jonczyk A, et al. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization. Nat Med. 1996;2:529–533
  43. Harari OA, Wickham TJ, Stocker CJ, et al. Targeting an adenoviral gene vector to cytokine-activated vascular endothelium via E-selectin. Gene Ther. 1999;6:801–807
  44. Havenga MJ, Lemckert AA, Grimbergen JM, et al. Improved adenovirus vectors for infection of cardiovascular tissues. J Virol. 2001;75:3335–3342
  45. Hedman M, Hartikainen J, Syvanne M, et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemai. Phase II results of the Kupoio Angiogenesis Trial (KAT). Circulation. 2003;107:2677–2683
  46. Hendrix RW. Evolution: the long evolutionary reach of viruses. Curr Biol. 1999;9:R914–R917
  47. Hida K, Klagsburn M. A new perspective on tumor endothelial cells: unexpected chromosome and centrosome abnormalities. Cancer Res. 2005;65:2507–2510
  48. Hood JD, Bednarski M, Frausto R, et al. Tumor regression by targeted gene delivery to the neovasculature. Science. 2002;296:2404–2407
  49. Hu P, Yan J, Sharifi J, et al. Comparison of three different targeted tissue factor fusion proteins for inducing tumor vessel thrombosis. Cancer Res. 2003;63:5046–5053
  50. Huang X, Molema G, King S, et al. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science. 1997;275:547–550
  51. Ivanenkov VV, Felici F, Menon AG. Targeted delivery of multivalent phage display vectors into mammalian cells. Biochim Biophys Acta. 1999;1448:463–472
  52. Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res. 1987;47:3039–3051
  53. Jin N, Chen W, Blazar B, et al. Gene therapy of murine solid tumors with T cells transduced with a retroviral vascular endothelial growth factor-immunotoxin target gene. Hum Gene Ther. 2002;13:497–508
  54. Kamal A, Boehm MF, Burrows FJ. Therapeutic and diagnostic implications of Hsp90 activation. Trends Mol Med. 2004;10:283–290
  55. Kay MA, Manno CS, Ragni MV, et al. Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet. 2000;24:257–261
  56. King DJ, Turner A, Farnsworth AP. Improved tumor targeting with chemically cross-linked recombinant antibody fragments. Cancer Res. 1994;54:6176–6185
  57. Koivunen E, Arap W, Valtanen H, et al. Tumor targeting with a selective gelatinase inhibitor. Nat Biotechnol. 1999;17:768–774
  58. Kolonin MG, Pasqualini R, Arap W. Molecular addresses in blood vessels as targets for therapy. Curr Opin Chem Biol. 2001;5:308–313
  59. Kolonin MG, Pasqualini R, Arap W. Teratogenicity induced by targeting a placental immunoglobulin transporter. Proc Natl Acad Sci U S A. 2002;99:13055–13060
  60. Kolonin MG, Saha PK, Chan L, et al. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004;10:625–632
  61. Kunath K, Merdan T, Hegener O. Integrin targeting using RGD–PEI conjugates for in vitro gene transfer. J Gene Med. 2003;5:588–599
  62. Larocca D, Witte A, Johnson W, et al. Targeting bacteriophage to mammalian cell surface receptors for gene delivery. Hum Gene Ther. 1998;9:2393–2399
  63. Larocca D, Kassner PD, Witte A, et al. Gene transfer to mammalian cells using genetically targeted filamentous bacteriophage. FASEB J. 1999;13:727–734
  64. Lee RT, Libby P. Matrix metalloproteinases: not-so-innocent bystanders in heart failure. J Clin Invest. 2000;106:827–828
  65. Lemarchand P, Jones M, Yamada I, et al. In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors. Circ Res. 1993;72:1132–1138
  66. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–874
  67. Lieber A. AAV display—homing in on the target. Nat Biotechnol. 2003;21:1011–1013
  68. Liu C, Bhattacharjee G, Boisvert W, et al. In vivo interrogation of the molecular display of atherosclerotic lesion surfaces. Am J Pathol. 2003;163:1859–1871
  69. Marchiò S, Lahdenranta J, Schlingemann RO. Aminopeptidase A is a functional target in angiogenic blood vessels. Cancer Cell. 2004;5:151–162
  70. Mari C, Strauss HW. Radiotracer characterization of coronary artery lesions. Nucl Med Commun. 2002;23:703–706
  71. Masood R, Gordon EM, Whitley MD, et al. Retroviral vectors bearing IgG-binding motifs for antibody-mediated targeting of vascular endothelial growth factor receptors. Int J Mol Med. 2001;8:335–343
  72. Mintz PJ, Kim J, Do KA, et al. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol. 2003;21:57–63
  73. Monaci P, Urbanelli L, Fontana L. Phage as gene delivery vectors. Curr Opin Mol Ther. 2001;3:159–169
  74. Muller O, Kaul F, Weitzman M, et al. Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nat Biotechnol. 2003;21:1040–1046
  75. Nicklin S, White S, Watkins S, et al. Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display. Circulation. 2000;102:231–237
  76. Nicklin S, Buening H, Dishart K, et al. Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells. Mol Ther. 2001;4:174–181
  77. Nicklin S, Baker A. Tropism-modified adenoviral and adeno-associated viral vectors for gene therapy. Curr Gene Ther. 2002;2:273–293
  78. Nicklin S, White S, Nicol C, et al. In vitro and in vivo characterisation of endothelial cell selective adenoviral vectors. J Gene Med. 2004;6:300–308
  79. Nilsson F, Kosmehl H, Zardi L, et al. Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. Cancer Res. 2001;61:711–716
  80. Oh P, Li Y, Yu J, et al. Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature. 2004;429:629–635
  81. Pajusola K, Gruchala M, Joch H, et al. Cell-type-specific characteristics modulate the transduction efficiency of adeno-associated virus type 2 and restrain infection of endothelial cells. J Virol. 2002;76:11530–11540
  82. Pasqualini R, Ruoslahti E. Organ targeting in vivo using phage display peptide libraries. Nature. 1996;380:364–366
  83. Pasqualini R, Koivunen E, Ruoslahti E. αv integrins as receptors for tumor targeting by circulating ligands. Nat Biotechnol. 1997;15:542–546
  84. Pasqualini R, Koivunen E, Kain R. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res. 2000;60:722–727
  85. Pasqualini R, Arap R, Rajotte W, et al. In vivo phage display. In:  Barbas CF,  Burton DR,  Scott JK, et al. editor. Phage display: a laboratory manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2000;p. 1–24chap 22
  86. Pentz RD, Flamm AL, Pasqualini R, et al. Revisiting ethical guidelines for research with terminal wean and brain-dead participants. Hastings Cent Rep. 2003;33:20–26
  87. Pentz RD, Cohen CB, Wicclair M, et al. Ethics guidelines for research with the recently dead. Nat Med. 2005;11:1145–1149
  88. Piersanti S, Cherubini G, Martina Y. Mammalian cell transduction and internalization properties of lambda phages displaying the full-length adenoviral penton base or its central domain. J Mol Med. 2004;82:467–476
  89. Poul MA, Marks JD. Targeted gene delivery to mammalian cells by filamentous bacteriophage. J Mol Biol. 1999;288:203–211
  90. Pulli T, Koivunen E, Hyypia T. Cell-surface interactions of echovirus 22. J Biol Chem. 1997;272:21176–21180
  91. Pyo R, Lee JK, Shipley JM, et al. Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest. 2000;105:1641–1649
  92. Rajotte D, Arap W, Hagedorn M, et al. Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. J Clin Invest. 1998;102:430–437
  93. Ran S, Gao B, Duffy S, et al. Infarction of solid Hodgkin's tumors in mice by antibody-directed targeting of tissue factor to tumor vasculature. Cancer Res. 1998;58:4646–4653
  94. Reynolds PN, Zinn KR, Gavrilyuk VD, et al. A targetable, injectable adenoviral vector for selective gene delivery to pulmonary endothelium in vivo. Mol Ther. 2000;2:562–578
  95. Richter M, Iwata A, Nyhuis J, et al. Adeno-associated virus vector transduction of vascular smooth muscle cells in vivo. Physiol Genomics. 2000;2:117–127
  96. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809
  97. Ross R. Atherosclerosis: current understanding of mechanisms and future strategies in therapy. Transplant Proc. 1993;25:2041–2043
  98. Ruf W, Rehemtulla A, Morrissey JH, et al. Phospholipid-independent and -dependent interactions required for tissue factor receptor and cofactor function. J Biol Chem. 1991;266:16256
  99. Savontaus MJ, Sauter BV, Huang TG, et al. Transcriptional targeting of conditionally replicating adenovirus to dividing endothelial cells. Gene Ther. 2002;9:972–979
  100. chiffelers RM, Ansari A, Xu J, et al. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acid Res. 2004;32:e149
  101. Scott JK, Smith GP. Searching for peptide ligands with an epitope library. Science. 1990;249:386–390
  102. Semenza GL. Surviving ischemia: adaptive responses mediated by hypoxia-inducible-factor-1. J Clin Invest. 2000;106:809–812
  103. Sengupta S, Eavarone D, Capila I, et al. Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature. 2005;436:568–572
  104. Shockley TR, Lin K, Nagy JA, et al. Penetration of tumor tissue by antibodies and other immunoproteins. Ann N Y Acad Sci. 1991;618:367–382
  105. Sipkins DA, Cheresh DA, Kazemi MR, et al. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med. 1998;4:623–626
  106. Suh W, Han SO, Yu L, et al. An angiogenic, endothelial-cell-targeted polymeric gene carrier. Mol Ther. 2002;6:664–672
  107. St Croix B, Rago C, Velculescu V, et al. Genes expressed in human tumor endothelium. Science. 2000;289:1197–1202
  108. Tarli L, Balza E, Viti F, et al. A high-affinity human antibody that targets tumoral blood vessels. Blood. 1999;94:192–198
  109. Tepe G, Duda SH, Meding J, et al. Tc-99m-labeled endothelin derivative for imaging of experimentally induced atherosclerosis. Atherosclerosis. 2001;157:383–392
  110. Thorpe PE, Burrows FJ. Antibody-directed targeting of the vasculature of solid tumors. Breast Cancer Res Treat. 1995;36:237–251
  111. Thorpe PE, Chaplin DJ, Blakey DC. The first international conference on vascular targeting: meeting overview. Cancer Res. 2003;63:1144–1147
  112. Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res. 2004;10:415–427
  113. Tran J, Master Z, Yu JL, et al. A role for surviving in chemoresistance of endothelial cells mediated by VEGF. Proc Natl Acad Sci U S A. 2002;99:4349–4354
  114. Trepel M, Grifman M, Weitzman MD, et al. Molecular adaptors for vascular-targeted adenoviral gene delivery. Hum Gene Ther. 2000;11:1971–1981
  115. Trepel M, Arap W, Pasqualini R. Exploring vascular heterogeneity for gene therapy targeting. Gene Ther. 2000;7:2059–2060
  116. Trepel M, Arap W, Pasqualini R. In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr Opin Chem Biol. 2002;6:399–404
  117. Veenendaal LM, Jin H, Ran S, et al. In vitro and in vivo studies of a VEGF121rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors. Proc Natl Acad Sci U S A. 2002;99:7866–7871
  118. Vidal CI, Mintz PJ, Lu K, et al. An HSP90-mimic peptide revealed by fingerprinting the pool of antibodies from ovarian cancer patients. Oncogene. 2004;23:8859–8867
  119. White S, Nicklin S, Buening H, et al. Gene delivery to vascular tissue in vivo by tropism-modified adeno-associated virus vectors. Circulation. 2004;109:513–519
  120. Wickham TJ, Mathias P, Cheresh DA. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell. 1993;73:309–319
  121. Wickham TJ, Haskard D, Segal D, et al. Targeting endothelium for gene therapy via receptors up-regulated during angiogenesis and inflammation. Cancer Immunol Immunother. 1997;45:149–151
  122. Wu AM, Chen W, Raubitschek A, et al. Tumor localization of anti-CEA single-chain Fvs: improved targeting by non-covalent dimers. Immunotechnology. 1996;2:21–36
  123. Yeager CL, Ashmun RA, Williams RK, et al. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992;357:420–422
  124. Yu JL, Rak JW, Coomber BL, et al. Effect of p53 status on tumor response to anti-angiogenic therapy. Science. 2002;295:1526–1528
  125. Zacher AN, Stock CA, Golden JW, et al. A new filamentous phage cloning vector: fd-tet. Gene. 1980;9:127–140
  126. Zurita AJ, Arap W, Pasqualini R. Mapping tumor vascular diversity by screening phage display libraries. J Control Release. 2003;91:183–186
  127. Zurita AJ, Troncoso P, Cardo-Vila M, et al. Combinatorial screenings in patients: the interleukin-11 receptor alpha as a candidate target in the progression of human prostate cancer. Cancer Res. 2004;64:435–439

PII: S1050-1738(06)00004-1

doi: 10.1016/j.tcm.2006.01.003

Trends in Cardiovascular Medicine
Volume 16, Issue 3 , Pages 80-88 , April 2006

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