Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature

Science

Volumn 275, Issue 5299, 1997, Pages 547-550

  Huang, Xianming ^a   Molema, Grietje ^a,c   King, Steven ^a   Watkins, Linda ^a   Edgington, Thomas S ^b   Thorpe, Philip E ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF GRONINGEN   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BISPECIFIC ANTIBODY; THROMBOPLASTIN;

ANIMAL MODEL; ANTIGEN BINDING; ARTICLE; CONTROLLED STUDY; HISTOPATHOLOGY; MOUSE; NEUROBLASTOMA; NONHUMAN; PRIORITY JOURNAL; TUMOR VASCULARIZATION; VASCULAR ENDOTHELIUM;

ANIMALS; ANTIBODIES; BLOOD COAGULATION; ENDOTHELIUM, VASCULAR; HISTOCOMPATIBILITY ANTIGENS CLASS II; HUMANS; IMMUNOCONJUGATES; INJECTIONS, INTRAVENOUS; MICE; MICE, INBRED BALB C; MICE, NUDE; NEUROBLASTOMA; THROMBOPLASTIN; TUMOR CELLS, CULTURED;

EID: 0031026481     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.275.5299.547     Document Type: Article

References (32)

1. J. Denekamp, Cancer Metastasis Rev. 9, 267 (1990).
2. R. K. Jain, Sci. Am. 271, 58 (July 1994).
3. E. W. Davie, K. Fujikawa, W. Kisiel, Biochemistry 30, 10363 (1991).
4. Human tTF (residues 1 to 219) was prepared as described [M. J. Stone, W. Ruf, D. J. Miles, T. S. Edgington, P. E. Wright, Biochem. J. 310, 605 (1995)].
5. W. Ruf, A. Rehemtulla, T. S. Edgington, J. Biol. Chem. 266, 2158 (1991).
6. L. R. Paborsky, I. W. Caras, K. L. Fisher, C. M. Gorman, ibid., p. 21911; R. Bach, R. Gentry, Y. Nemerson, Biochemistry 25, 4007 (1986); S. Krishnaswamy, K. A. Field, T. S. Edgington, J. Biol. Chem. 267, 26110 (1992).
7. L. R. Paborsky, I. W. Caras, K. L. Fisher, C. M. Gorman, ibid., p. 21911; R. Bach, R. Gentry, Y. Nemerson, Biochemistry 25, 4007 (1986); S. Krishnaswamy, K. A. Field, T. S. Edgington, J. Biol. Chem. 267, 26110 (1992).
8. L. R. Paborsky, I. W. Caras, K. L. Fisher, C. M. Gorman, ibid., p. 21911; R. Bach, R. Gentry, Y. Nemerson, Biochemistry 25, 4007 (1986); S. Krishnaswamy, K. A. Field, T. S. Edgington, J. Biol. Chem. 267, 26110 (1992).
9. d-expressing intestinal epithelium.
10. d antigen, was purchased from the American Type Culture Collection. The CAMPATH-2 antibody is a rat IgG2b antibody to human CD7. The TF9-10H10 antibody (herein referred to as 10H10) is a mouse IgG1 nonneutralizing antibody to human TF [J. H. Morrissey, D. S. Fair, T. S. Edgington, Thromb. Res. 52, 247 (1988)]. The MRC OX7 hybridoma (herein referred to as OX7) secretes a mouse IgG1 antibody that recognizes the Thy 1.1 antigen. The bispecific antibodies B21-2/10H10, CAMPATH-2/10H10, OX7/10H10, and B21-2/OX7 were synthesized as described [M. Brennan, P. F. Davison, H. Paulus, Science 229, 81 (1985)].
11. d antigen, was purchased from the American Type Culture Collection. The CAMPATH-2 antibody is a rat IgG2b antibody to human CD7. The TF9-10H10 antibody (herein referred to as 10H10) is a mouse IgG1 nonneutralizing antibody to human TF [J. H. Morrissey, D. S. Fair, T. S. Edgington, Thromb. Res. 52, 247 (1988)]. The MRC OX7 hybridoma (herein referred to as OX7) secretes a mouse IgG1 antibody that recognizes the Thy 1.1 antigen. The bispecific antibodies B21-2/10H10, CAMPATH-2/10H10, OX7/10H10, and B21-2/OX7 were synthesized as described [M. Brennan, P. F. Davison, H. Paulus, Science 229, 81 (1985)].
12. 7 C1300(Muγ) cells subcutaneously into the right anterior flank of BALB/c nu/nu mice (Charles River Labs, Wilmington, MA). When the tumors had grown to ∼0.8 cm in diameter, mice were randomly assigned to different experimental groups, each containing four to nine mice. Coaguligands were prepared by mixing bispecific antibodies (150 μg) and tTF (125 μg) in a total volume of 2.5 ml of 0.9% NaCl and incubating at 4°C for 1 hour. Mice received intravenous injections of 0.25 ml of this mixture per 25 g of body weight (that is, 0.6 mg/kg of bispecific antibody plus 0.5 mg/kg of tTF). Other mice received equivalent doses of bispecific antibodies or tTF alone. The injections were performed over ∼45 s into one of the tail veins, followed by 200 μl of saline. In the tumor growth-inhibition experiments, the infusions were repeated 6 days later. Perpendicular tumor diameters were measured at regular intervals and tumor volumes were calculated. Differences in tumor volume were tested for statistical significance with the Mann-Whitney rank sum test for two independent samples. For histopathologic analyses, mice were anesthetized with metophane at various intervals after treatment and were exsanguinated by perfusion with heparinized saline. Tumors and normal tissues were excised and immediately fixed in 3% (v/v) formalin. Paraffin sections were cut and stained with hematoxylin and eosin or with Martius Scarlet Blue trichrome for the detection of fibrin. Animal care in all experiments was in accordance with institutional guidelines.
13. L. B. Zacharski et al., J. Natl. Cancer Inst. 85, 1225 (1993); J. C. Murray, M. Clauss, G. Thurston, D. Stern, Int. J. Radiat. Biol. 60, 273 (1991).
14. L. B. Zacharski et al., J. Natl. Cancer Inst. 85, 1225 (1993); J. C. Murray, M. Clauss, G. Thurston, D. Stern, Int. J. Radiat. Biol. 60, 273 (1991).
15. At the treatment dose of 0.6 mg/kg B21-2/10H10 plus 0.5 mg/kg tTF, toxicity was observed in only 2 of 40 mice (thrombosis of the tail vein). The tTF itself was not toxic at 1.28 mg/kg when given intravenously.
16. S. King and P. E. Thorpe, unpublished data.
17. F. J. Burrows and P. E. Thorpe, Proc. Natl. Acad. Sci. U.S.A. 90, 8996 (1993); F. J. Burrows and P. E. Thorpe, Pharmacol. Ther. 64, 155 (1994).
18. F. J. Burrows and P. E. Thorpe, Proc. Natl. Acad. Sci. U.S.A. 90, 8996 (1993); F. J. Burrows and P. E. Thorpe, Pharmacol. Ther. 64, 155 (1994).
19. F. J. Burrows, Y. Watanabe, P. E. Thorpe, Cancer Res. 52, 595 (1992).
20. J. Folkman, Semin. Cancer Biol. 3, 65 (1992).
21. F. J. Burrows et al., Clin. Cancer Res. 1, 1623 (1995).
22. W. J. Rettig et al., Proc. Natl. Acad. Sci. U.S.A. 89, 10832 (1992).
23. J. M. Wang et al., Int. J. Cancer 54, 363 (1993).
24. B. Carnemolla et al., J. Cell Biol. 108, 1139 (1989).
25. O. S. Bruland, O. Fodstad, A. E. Stenwig, A. Pihl, Cancer Res. 48, 5302 (1988).
26. R. O. Schlingemann et al., Lab. Invest. 62, 690 (1990).
27. W. Paulus, E. H. Sage, U. Liszka, M. L. Iruela-Arispe, K. Jellinger, Br. J. Cancer 63, 367 (1991).
28. K. H. Plate, G. Breier, B. Millauer, A. Ullrich, W. Risau, Cancer Res. 53, 5822 (1993); L. F. Brown et al., ibid., p. 4727.
29. K. H. Plate, G. Breier, B. Millauer, A. Ullrich, W. Risau, Cancer Res. 53, 5822 (1993); L. F. Brown et al., ibid., p. 4727.
30. H. F. Dvorak et al., J. Exp. Med. 174, 1275 (1991).
31. M. Trucco and S. dePetris, in Immunological Methods, I. Lefkovits and B. Pernis, Eds. (Academic Press, New York, 1981), vol. 2, p. 1.
32. We thank G. Hale for CAMPATH-2, A. F. Williams for the OX7 hybridoma, A. Gilman for comments on the manuscript and for support, E. Derbyshire and C. Gottstein for discussions, J. Overholser for technical assistance, W. Ruf for tTF, and K. Schiller for help in manuscript preparation. Supported in part by grants from the Pardee Foundation and NIH (RO1-CA59569, RO1-CA54168, and PO1-HL16411).