Skip to main content
SpringerLink
Log in

Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia developed in severe combined immune-deficient mice

  • Published:
Cell Biophysics Aims and scope Submit manuscript

Abstract

The transplantation of the human T-cell acute lymphoblastic leukemia (T-ALL) cell line HSB-2 into severe combined immune-deficient (SCID) mice was found to produce a disseminated pattern of leukemia similar to that seen in humans. The iv injection of 107 HSB-2 cells was associated with a universally fatal leukemia. Histopathological examination of animals revealed the spread of leukemia initially from bone marrow to involve all major organs including the meninges.

An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 monoclonal antibody (MAb) HB2 to the ribosome inactivating protein (RIP) saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT) to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. In an in vivo study, the IT was shown to significantly prolong the survival of SCID mice injected with HSB-2 cells compared to untreated control animals. This therapeutic effect was seen both with a single injection of 10 μg of IT given 7 d after the injection of HSB-2 cells, and was even more effective when IT was administered as three daily injections of 10 μg on d 7, 8, and 9. These results demonstrate the useful application of human leukemia xenografts in SCID mice and the potential therapeutic effect of an anti-CD7 IT in human T-ALL.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fogh, J., Fogh, J. M., and Orfeo, T. (1977)J. Natl. Cancer Inst. 59, 221–226.

    PubMed  CAS  Google Scholar 

  2. Giovanella, B. C., Stehlin, J. S., Jr., Williams, L. J., Jr., Lee, S. S., and Shepard, R. C. (1978)Cancer 42, 2269–2281.

    Article  PubMed  CAS  Google Scholar 

  3. Watanabe, S., Shimosato, Y., Kameya, T., Kuroki, M., Kitahara, T., Minato, K., and Shimoyama, M. (1978)Cancer Res. 38, 3494–3498.

    PubMed  CAS  Google Scholar 

  4. Watanabe, S., Shimosato, Y., Kuroki, M., Sato, Y., and Nakajima, T. (1980)Cancer Res. 40, 2588–2592.

    PubMed  CAS  Google Scholar 

  5. Bosma, G. C., Custer, R. P., and Bosma, M. J. (1983)Nature 301, 527–530.

    Article  PubMed  CAS  Google Scholar 

  6. McCune, J. M., Namikawa, R., Kaneshima, H., Shultz, L. D., Lieberman, M., and Weissman, I. L. (1988)Science 241, 1632–1639.

    Article  PubMed  CAS  Google Scholar 

  7. Mosier, D. E., Gulizia, R. J., Baird, S. M., and Wilson, D. B. (1988)Nature 335, 256–259.

    Article  PubMed  CAS  Google Scholar 

  8. Mosier, D. E. (1990)J. Clin. Immunol. 10, 185–191.

    Article  PubMed  CAS  Google Scholar 

  9. Kamel-Reid, S., and Dick, J. E. (1988)Science 242, 1706–1709.

    Article  PubMed  CAS  Google Scholar 

  10. Namikawa, R., Kaneshima, H., Lieberman, M., Weissman, I. L., and McCune, J. M. (1988)Science 242, 1684–1686.

    Article  PubMed  CAS  Google Scholar 

  11. McCune, J. M., Namikawa, R., Shih, C.-C., Rabin, L., and Kaneshima, H. (1990)Science 247, 564–566.

    Article  PubMed  CAS  Google Scholar 

  12. Kamel-Reid, S., Letarte, M., Sirard, C., Doedens, M., Grunberger, T., Fulop, G., Freedman, M. H., Phillips, R. A., and Dick, J. E. (1989)Science 246, 1597–1600.

    Article  PubMed  CAS  Google Scholar 

  13. Ghetie, M.-A., Tucker, T., Jones, D., Uhr, J. W., and Vitetta, E. S. (1990)Int. J. Cancer 45, 481–485.

    Article  PubMed  CAS  Google Scholar 

  14. Cesano, A., O'Connor, R., Lange, B., Finan, J., Rovera, G., and Santoli, D. (1991)Blood 77, 2463–2474.

    PubMed  CAS  Google Scholar 

  15. Kamel-Reid, S., Letarte, M., Doedens, M., Greaves, A., Murdoch, B., Grunberger, T., Lapidot, T., Thorner, P., Freedman, M. H., Phillips, R. A., and Dick, J. E. (1991)Blood 78, 2973–2981.

    PubMed  CAS  Google Scholar 

  16. Jansen, B., Uckun, F. M., Jaszcz, W. B., and Kersey, J. H. (1992)Cancer Res. 52, 406–412.

    PubMed  CAS  Google Scholar 

  17. Uckun, F. M., Chelstrom, L. M., Finnegan, D., Tuel-Ahlgren, L., Manivel, C., Irvin, J. D., Myers, D. E., and Gunther, R. (1992)Blood 79, 3116–3129.

    PubMed  CAS  Google Scholar 

  18. Purtillo, D. T., Falk, K., Pirruccello, S. J., Nakamine, H., Kleveland, K., Davis, J. R., Okano, M., Taguchi, Y., Sanger, W. G., and Beisel, K. W. (1991)Int. J. Cancer 47, 510–517.

    Article  Google Scholar 

  19. Cannon, M. J., Pisa, P., Fox, R. I., and Cooper, R. I. (1990)J. Clin. Invest. 85, 1333–1337.

    Article  PubMed  CAS  Google Scholar 

  20. Rowe, M., Young, L. S., Crocker, J., Stokes, H., Henderson, S., and Rickinson, A. B. (1991)J. Exp. Med. 173, 147–158.

    Article  PubMed  CAS  Google Scholar 

  21. Charley, M. R., Tharp, M., Locker, J., Deng, J.-S., Golsen, J. B., Mauro, T., McCoy, P., Abell, E., and Jegasothy, B. (1990)J. Invest. Dermatol. 94, 381–384.

    Article  PubMed  CAS  Google Scholar 

  22. Waller, E. K., Kamel, O. W., Cleary, M. L., Majumdar, A. S., Schick, M. R., Lieberman, M., and Weissman, I. L. (1991)Blood 78, 2650–2665.

    PubMed  CAS  Google Scholar 

  23. Reddy, S., Piccione, D., Takita, H., and Bankert, R. B. (1987)Cancer Res. 47, 2456–2460.

    PubMed  CAS  Google Scholar 

  24. Adams, R. A., Pothier, L., Flowers, A., Lazarus, H., Farber, S., and Foley, G. E. (1970)Exp. Cell Res. 62, 5–10.

    Article  PubMed  CAS  Google Scholar 

  25. Stirpe, F., Gasperi-Campani, G., Barbieri, L., Falasca, A., Abbondanza, A., and Stevens, W. A. (1983)Biochem. J. 216, 617–625.

    PubMed  CAS  Google Scholar 

  26. Thorpe, P. E., Brown, A. N. F., Bremmer, J. A. G., Jr., Foxwell, B. M. J., and Stirpe, F. (1985)J. Natl. Cancer. Inst. 75, 151–159.

    PubMed  CAS  Google Scholar 

  27. Flavell, D. J., Cooper, S., Morland, B., and Flavell, S. U. (1991)Br. J. Cancer 64, 274–280.

    PubMed  CAS  Google Scholar 

  28. Dorshkind, K., Pollack, S. B., Bosma, M. J., and Phillips, R. A. (1985)J. Immunol. 134, 3798–3801.

    PubMed  CAS  Google Scholar 

  29. Dillman, R. O., Johnson, D. E., Shawler, D. L., Halpern, S. E., Leonard, J. E., and Hagan, P. L. (1985)Cancer Res. 45, 5632–5636.

    PubMed  CAS  Google Scholar 

  30. Myers, C. D., Thorpe, P. E., Ross, W. C. J., Cumber, A. S., Katz, F. E., and Greaves, M. F. (1984)Blood 63, 1178–1184.

    PubMed  CAS  Google Scholar 

  31. Vallera, D. A., Ash, R. C., Zanjani, E. D., Kersey, J. H., Lebien, T. W., Beverley, P. C. L., Neville, D. M., and Youle, R. J. (1983)Science 222, 512–515.

    Article  PubMed  CAS  Google Scholar 

  32. Fishwild, D. M., Aberle, S., Bernhard, S. L., and Kung, A. H. C. (1992)Cancer Res. 52, 3056–3062.

    PubMed  CAS  Google Scholar 

  33. Ramakrishnan, S. and Houston, L. L. (1984)Science 223, 58–61.

    Article  PubMed  CAS  Google Scholar 

  34. Youle, R. J. and Neville, D. M., Jr. (1982)J. Biol. Chem. 257, 1598–1601.

    PubMed  CAS  Google Scholar 

  35. Leonard, J. E., Johnson, D. E., Shawler, D. L., and Dillman, R. O. (1988)Cancer Res. 48, 4862–4867.

    PubMed  CAS  Google Scholar 

  36. Weil-Hillman, G., Uckun, F. M., Manske, J. M., and Vallera, D. A. (1987)Cancer Res. 47, 579–585.

    PubMed  CAS  Google Scholar 

  37. Jansen, B., Vallera, D. A., Jaszcz, W. B., Nguyen, D., and Kersey, J. H. (1992)Cancer Res. 52, 1314–1321.

    PubMed  CAS  Google Scholar 

  38. Uckun, F. M., Kersey, J. H., Vallera, D. A., Ledbetter, J. A., Wesdorf, D., Myers, D. E., Haake, R., and Ramsay, N. K. C. (1990)Blood 76, 1723–1733.

    PubMed  CAS  Google Scholar 

  39. Laurent, G., Pris, J., Farcet, J.-P., Carayon, P., Blythman, H., Casellas, P., Poncelet, P., and Jansen, F. K. (1986)Blood 67, 1680–1687.

    PubMed  CAS  Google Scholar 

  40. Vitteta, E. S., Stone, M., Amlot, P., Fay, J., May, R., Till, M., Newman, J., Clark, P., Collins, R., Cunningham, D., Ghetie, V., Uhr, J. W., and Thorpe, P. E. (1991)Cancer Res. 51, 4052–4058.

    Google Scholar 

  41. Uckun, F. M., Manivel, C., Arthur, D., Chelstrom, L. M., Finnegan, D., Tuel-Ahlgern, L., Irvin, J. D., Myers, D. E., and Gunther, R. (1992)Blood 79, 2201–2214.

    PubMed  CAS  Google Scholar 

  42. Grossbard, M. L., Freedman, A. S., Ritz, J., Coral, F., Goldmacher, V. S., Eliseo, L., Spector, N., Dear, K., Lambert, J. M., Blättler, W. A., Epstein, C. L., and Nadler, L. M. (1992)Blood 79, 576–585.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Simon Flavell Leukaemia Research Laboratory, Southampton General Hospital, SO9 4XY, Southampton, UK

    B. J. Morland, D. Boehm, S. U. Flavell & D. J. Flavell

  2. Department of Child Health, Southampton General Hospital, Southampton, UK

    J. A. Kohler

Authors
  1. B. J. Morland
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Boehm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. U. Flavell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. A. Kohler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. J. Flavell
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morland, B.J., Boehm, D., Flavell, S.U. et al. Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia developed in severe combined immune-deficient mice. Cell Biophysics 24, 315–329 (1994). https://doi.org/10.1007/BF02789243

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02789243

Index Entries

Search

Navigation