SpringerLink
Log in

Targeting Vascular Endothelium with Antibodies

  • Chapter
Tumor Targeting in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 249 Accesses

Abstract

Despite the recent progress in the management of cancer, the majority of metastatic solid tumors are not curable by current treatment modalities. In 1996 in the United States alone 500,000 people died as a result of metastatic cancer (1). There are many reasons for the inability to eradicate malignant neoplasms by conventional cytotoxic drugs. Chemotherapy is not specific against cancer, but targets all rapidly proliferating cells by inhibiting DNA synthesis or interfering with different pathways of cell division and metabolism. It is frequently associated with significant dose-limiting side effects related to toxicity to normally dividing cells in the bone marrow, skin, and gastrointestinal mucosa. In addition, neoplastic cells exhibit profound genetic instability, and over a period of time, accumulate genetic mutations that enhance their metastatic potential and render them resistant to chemotherapeutic agents (2). The inadequate efficacy and severe side effects of standard chemotherapy regimens have driven the search for novel approaches to anticancer therapy, particularly for the treatment of metastatic tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (Canada)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. American Cancer Society. Cancer facts and figures, 1997. American Cancer Society, New York, 1997.

    Google Scholar 

  2. Simon SM, Schinder M. Cell biological mechanisms of multidrug resistance in tumors. Proc Natl Acad Sci USA 1994; 91:3497–3504.

    Article  PubMed  CAS  Google Scholar 

  3. Folkman J, Shing Y, Angiogenesis. J Biol Chem 1992; 267:10931–10934.

    PubMed  CAS  Google Scholar 

  4. Liotta L, Steeg PS, Stetler-Stevensen WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991; 64:327–336.

    Article  PubMed  CAS  Google Scholar 

  5. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992; 267:10931–10934.

    PubMed  CAS  Google Scholar 

  6. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nature Med 1995; 1:27–31.

    Article  PubMed  CAS  Google Scholar 

  7. Lichtenbeld HHC, van Dam-Mieras MCE, Hillen HFP. Tumor angiogenesis: pathophysiology and clinical significance. Netherlands J Med 1996; 49:42–51.

    Article  CAS  Google Scholar 

  8. Folkman J, Klagsburn M. Angiogenic factors. Science 1987; 235:442–447.

    Article  PubMed  CAS  Google Scholar 

  9. Gabrilovich D, Chen H, Girgis K, Cunningham H, Meny G, Nadaf S, et al. Production of vascular endothelila growth factor by human tumors inhibits the functional maturation of dendritic cells. Nature Med 1996; 2:1096–1103.

    Article  PubMed  CAS  Google Scholar 

  10. Ferrara N. Vascular endothelial growth factor: molecular and biological aspects. Curr Top Microbiol Immunol 1999; 237:1–30.

    Article  PubMed  CAS  Google Scholar 

  11. Ulrich A, Schlesinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990; 61:203–212.

    Article  Google Scholar 

  12. Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumor angiogenesis factor in human glioma in vivo. Nature 1992; 359:845–848.

    Article  PubMed  CAS  Google Scholar 

  13. Plate KH, Breier G, Weich HA, Mennel HD, Risau W. Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Intl J Cancer 1994; 59:520–529.

    Article  CAS  Google Scholar 

  14. Yoshiji H, Gomez DE, Shibuya M, Thorgeirsson UP. Expression of vascular endothelial growth factor, its receptors and other angiogenic factors in human breast cancer. Cancer Res 1996; 56:2013–2016.

    PubMed  CAS  Google Scholar 

  15. O’Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL. Different angiogenic pathways characterize superficial and invasive bladder cancers. Cancer Res 1995; 55:510–513.

    PubMed  Google Scholar 

  16. Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 1995; 95:1789–1797.

    Article  PubMed  CAS  Google Scholar 

  17. Takahashi Y, Kitadai Y, Bukana CD, Cleary KR, Ellis LM. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 1995; 55:3964–3968.

    PubMed  CAS  Google Scholar 

  18. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 1993; 53:4727–4735.

    PubMed  CAS  Google Scholar 

  19. Toi M, Hoshina S, Takayanagi T, Tominaga T. Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn J Cancer Res 1994; 85:1045–1049.

    Article  PubMed  CAS  Google Scholar 

  20. Anan K, Morisaki T, Katano M, Ikubo A, Kitsuki H, Uchiyama A, Kuroki S, Tanaka M, Torisu M. Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer. Surgery 1996; 119:333–339.

    Article  PubMed  CAS  Google Scholar 

  21. Takahashi A, Sasaki H, Kim SJ, Tobisu K, Kakizoe T, Tsukamoto T, et al. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res 1994; 54:4233–4237.

    PubMed  CAS  Google Scholar 

  22. Rockwell P, Neufeld G, Glassman A, Caron D, Goldstein N. In vitro neutralization of vascular endothelial growth factor activation of Flk-1 by a monoclonal antibody. Mol Cell Diff 1995; 3:91–109.

    CAS  Google Scholar 

  23. Cushman C, Escobedo J, Parry TJ, Kisich KO, Richardson ML, Speirer KS, et al. Ribozyme inhibition of VEGF-mediated endothelial cell proliferation in cell culture and VEGF-induced angiogenesis in a rat corneal model. Abstract from Angiogenesis Inhibitors and Other Novel Therapeutic Strategies for Ocular Diseases of Neovascularization.

    Google Scholar 

  24. Kim KJ, Li B, Winer J, Armanini N, Gillett N, Philips HS, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 1993; 362:841–844.

    Article  PubMed  CAS  Google Scholar 

  25. Asano M, Yukita A, Matsumoto T, Kondo S, Suzuki H. Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor 121. Cancer Res 1995; 55:5296–5301.

    PubMed  CAS  Google Scholar 

  26. Folkman J. Tumor angiogenesis, in The Molecular Basis of Cancer (Mendelsohn J, Howley PM, Israel MA, Liotta LA, ed). WB Saunders, Philadelphia, 1995, pp 206–232.

    Google Scholar 

  27. Lichtenbeld HHC, van Dam-Mieras MCE, Hillen HFP. Tumor angiogenesis: pathophysiology and clinical significance. Neth J Med 1996; 49:42–51.

    Article  PubMed  CAS  Google Scholar 

  28. Dameron K, Bouck N. Control of angiogenesis in fibroblasts by p-53 regulation of thrombospondin-1. Science 1994; 265:582–584.

    Article  Google Scholar 

  29. Gnarra JR, Zhou S, Merrill MJ, et al. Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc Natl Acad Sci USA 1996; 93:10589–10593.

    Article  PubMed  CAS  Google Scholar 

  30. O’Reilly MS, Holmgren M, Shing Y, Chen C, Rosenthal RA, Folkman J, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79:315–328.

    Article  PubMed  Google Scholar 

  31. O’Reilly MS, Boehma T, Shing Y, Fukai N, Vasios G, Folkman J, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88:277–285.

    Article  PubMed  Google Scholar 

  32. Brooks PC. Role of integrins in angiogenesis. Eur J Cancer 1996; 32A:2423–2429.

    Article  Google Scholar 

  33. Brooks PC. Functional cooperation of integrin alpha v beta 3 and the matrix metalloproteinase (MMP-2) in angiogenesis. Fourth International Conference on Angiogenesis Targets 1997, June, San Francisco, CA.

    Google Scholar 

  34. O’Reilly MS, Boehm T, Sing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88:277–285.

    Article  PubMed  Google Scholar 

  35. Boehm T, Folkman J, Browder T, O’Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997; 390:404–407.

    Article  PubMed  CAS  Google Scholar 

  36. Kerbel RS. A cancer therapy resistant to resistance. Nature 1997; 390:335–336.

    Article  PubMed  CAS  Google Scholar 

  37. Teicher BA, Holden SA, Dupuis NP, et al. Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma. Breast Cancer Res Treat 1995; 36:227–236.

    Article  PubMed  CAS  Google Scholar 

  38. Kato K, Kakinuma H, Matsuda Y. Enhanced suppression of tumor growth by combination of angiogenesis inhibitor O-(chloroacetyl-carbamoyl) fumagillol (TNP-470) and cytotoxic agents in mice. Cancer Res 1994; 54:5143–5147.

    PubMed  CAS  Google Scholar 

  39. Browder T, Butterfield CE, Krailing BM, Shi B, Marshall B, O’Reilly M, Folkman J. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000; 60(7):1878–1886.

    PubMed  CAS  Google Scholar 

  40. Burrows FJ, Overhoiser JP, Thorpe PE. Potent antitumor effects of an antitumor endothelial cell immunotoxin in a murine vascular targeting model. Cell Biophys 1994; 24–25:15–25.

    PubMed  Google Scholar 

  41. Huang X, Molema G, King S, Watkins L, Edgington TS, Thorpe P. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science 1997; 275(5299):547–550.

    Article  PubMed  CAS  Google Scholar 

  42. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma. N Engl J Med 1991; 324:1–8.

    Article  PubMed  CAS  Google Scholar 

  43. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early stage breast carcinoma. J Natl Cancer Inst 1992; 84:1875–1887.

    Article  PubMed  CAS  Google Scholar 

  44. Horak ER, Leek R, Klenk N, et al. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 1992; 340:1120–1124.

    Article  PubMed  CAS  Google Scholar 

  45. Williams JK, Carlson GW, Cohen C, Derose PB, Hunter S, Jurkiewicz MJ. Tumor angiogenesis as a prognostic factor in oral cavity tumors. Am J Surg 1994; 168:373–380.

    Article  PubMed  CAS  Google Scholar 

  46. Dickinson AJ, Fox SB, Persad RA, Hollyer J, Sibley GN, Harris AL. Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas. Br J Urol 1994; 74:762–766.

    Article  PubMed  CAS  Google Scholar 

  47. Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD. Detection of tumor angiogenesis in vivo by alpha v beta 3-targeted magnetic resonance imaging. Nature Medicine 1998; (5):623–626.

    Article  Google Scholar 

  48. Melnyk O, Zimmerman M, ** Kim K, Shuman M. Neutralizing Anti-vascular endothelial growth factor antibody inhibits further growth of established prostate cancer and metastases in preclinical model. J Urol 1999; 161:960–963.

    Article  PubMed  CAS  Google Scholar 

  49. Asano M, Yukita A, Suzuki H. Wide spectrum of antitumor activity of a neutralizing monoclonal antibody to human vascular endothelial growth factor. Jpn J Cancer Res 1999; 90(1):93–100.

    Article  PubMed  CAS  Google Scholar 

  50. Gorski DH, Beckett MA, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor efects of ionizing radiation. Cancer Res 1999; 59(14):3374–3378.

    PubMed  CAS  Google Scholar 

  51. Gabrilovich D, Ishida T, Nadaf S, Ohm J, Corbone D. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res 1999; 5:2963–2970.

    PubMed  CAS  Google Scholar 

  52. Gordon M, Talpaz M, Margolin K, Holmgren E, Sledge G, Benjamin R, et al. Phase I trial of recombinant humanized monoclonal anti-vascular endothelial growth factor (Anti-VEGF MAbB in patients with metastatic cancer). Proc Am Soc Clin Oncol 1998; 17 (Abstr #809).

    Google Scholar 

  53. Margolin K, Gordon MS, Holmgren E, Gaudreault J, et al. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J Clin Oncol 2001; 19(3):851–856.

    PubMed  CAS  Google Scholar 

  54. DeVore RF, Fehrenbacher L, Herbst RS, Langer CJ, Kelly K, Gaudreault J, et al. A randomized Phase II trial comparing rhumab VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus carboplatin/paclitaxelo (CP) to CP alone in patients with Stage IIIB/IV NSCLC. Proc Am Soc Clin Oncol 2000; vol 19 (Abstr #1896).

    Google Scholar 

  55. Bergsland E, Hurwitz H, Fehrenbacher L, Meropol N, Novotny W, Gaudreault J, et al. A randomized Phase II trial comparing rhuMAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus 5-fluorouracil/leucovorin (FU/LV) to FU/LV alone patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 2000; vol 19 (Abstr #939).

    Google Scholar 

  56. Sledge G, Miller K, Novotny W, Gaudreault J, Ash M, Colbleigh M. A Phase II trial of single-agent rhuMAb VEGF (recombinant monoclonal antibody to vascular endothelial cell growth factor) in patients with relapsed metastatic breast cancer. Proc Am Soc Clin Oncol 2000; 19(Abstr #5C).

    Google Scholar 

  57. Klotz O, Park JK, Pleyer U, Hartmann C, Baatz H. Inhibition of corneal neovascularization by alpha v integrin antagonist in the rat. Graefes Arch Clin Exp Ophthalmol 2000; 1:88–93.

    Article  Google Scholar 

  58. Brooks PC, Stromblad S, Klemke R, Visscher D, Sarkar FH, Cheresh DA. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. J Clin Invest 1995; 4:1815–22.

    Article  Google Scholar 

  59. Gutheil JC, Campbell TN, Pierce PR, Watkins JD, Huse WD, Bodkin DJ, et al. Phase I study of Vitaxin, an anti-angiogenic humanized monoclonal antibody to vascular integrin alpha v beta 3. Proc Am Soc Clin Oncol 1998 (Abstr #832).

    Google Scholar 

  60. Patel SR, Jenkins J, Papadopulos NE, Burgess MA, Plager C, Charnsagavei C, et al. A pilot study of an angiogenesis inhibitor Vitaxin in patients with advanced leiomyosarcomas. Proc Am Soc Clin Oncol 2000, (Abstr #2202).

    Google Scholar 

  61. Prewett M, Huber J, Li Yiwen, Santiago A, O’Connor A, King K, et al. Antivascular endothelial growth factor receptor (Fetal Liver Kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 1999; 59:5209–5218.

    PubMed  CAS  Google Scholar 

  62. Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, Kerbel RS. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 2000; 105(8):15–24.

    Article  Google Scholar 

  63. Zhu Z, Witte L, Hicklin D, Bohlen P, Ludwig D, Lutty G, et al. Safety profile in primates and antiangiogenic activity in murine and canine models of a chimeric antibody directed against the vascular endothelial growth factor receptor 2. Proc Am Soc Clin Oncol 2000; (Abstr #1793).

    Google Scholar 

  64. Brekken RA, Huang X, King SW, Thorpe PE. Vascular endothelial growth factor as a marker of tumor endothelium. Cancer Res 1998; 58(9):1952–1959.

    PubMed  CAS  Google Scholar 

  65. Aonuma M, Yoshitake Y, Nishikawa K, Tanaka N. Different antitumor activities of anti-bFGF neutralizing antibodies:heparin binding domain provides an inefficient epitope for neutralization in vivo. Anticancer Res 1999; 19:4039–4044.

    PubMed  CAS  Google Scholar 

  66. Piccoli R, Olson K, Vallee B, Pett J. Chimeric anti-angiogenin antibody cAb 26–2F inhibits the formation of human breast cancer xenografts in athymic mice. Proc Natl Acad Sci USA 1998; 95:4579–4583.

    Article  PubMed  CAS  Google Scholar 

  67. Tarli L, Balza E, Viti F, Borsi L, Castellani P, Berndorff D, et al. A high affinity human antibody that targets tumoral blood vessels. Blood 1999; 94(1):192–198.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Przemek Twardowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kim Margolin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Université Laval, Sainte-Foy, Québec, Canada

    Michel Pagé PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Twardowski, P., Margolin, K. (2002). Targeting Vascular Endothelium with Antibodies. In: Pagé, M. (eds) Tumor Targeting in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-167-1_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-167-1_9

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-251-3

  • Online ISBN: 978-1-59259-167-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation