Skip to main content
SpringerLink
Log in

Interferon-α conjugation to human osteogenic sarcoma monoclonal antibody 791T/36

  • Original Articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Human lymphoblastoid interferon-α (IFN-α) has been coupled using N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) to a murine monoclonal antibody (791T/36) which reacts with antigens expressed on human osteogenic sarcomas. The purified conjugates retain antibody activity as defined by their capacity to compete with binding of fluorescein isothiocyanate-labelled 791T/36 antibody to 791T cells. IFN-α-791T/36 antibody conjugates synthesized with 125I-trace-labelled IFN-α and 131I-trace-labelled antibody also bound to 791T cells, but not to bladder carcinoma T24 cells. The conjugates also retain the capacity of free IFN to activate natural killer cells in human peripheral blood lymphocytes and show specific localization in human osteogenic sarcoma xenografts developing in immunodeprived mice. These findings establish that conjugates containing IFN linked to a monoclonal antibody reacting with osteogenic sarcoma-associated antigens have potential for targeted immunotherapy and in related investigations with antibody has been shown by gamma camera imaging of patients following infusion of 131I-labelled antibody to localize in primary osteogenic sarcomas.

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. Allen G, Fantes KH, Burke DC, Morser J (1982) Analysis and purification of human lymphoblastoid (Namalwa) interferon using a monoclonal antibody. J Gen Virol 63:207

    Google Scholar 

  2. Baldwin RW (1982) Monoclonal antibodies in the diagnosis, detection and therapy of cancer. Proc R Soc Edin 81B:261

    Google Scholar 

  3. Baldwin RW, Byers VS (1980) Immunoregulation by bacterial organisms and their role in the immunotherapy of cancer. In: Chedid L, Miescher PA, Mueller-Eberhard HJ (eds) Immunostimulation. Springer, Berlin Heidelberg New York, pp 73–94

    Google Scholar 

  4. Baldwin RW, Pimm MV (1982) BCG-mediated host responses in tumour immunotherapy. In: Jeljaszewicz J, Pulverer G, Roskowski W (eds) Bacteria and Cancer. Academic Press, London, pp 205

    Google Scholar 

  5. Baldwin RW, Pimm MV (1983) Anti-tumour monoclonal antibodies for radioimmunodetection of tumors and drug targeting. Cancer Metastasis Reviews 2:89

    Google Scholar 

  6. Baldwin RW, Flannery GR, Pelham JM, Gray JD (1982) Immunomodulation by IFN-conjugated monoclonal antibody to human osteogenic sarcoma. Proc Am Assoc Cancer Res 23:254

    Google Scholar 

  7. Baldwin RW, Pimm MV, Embleton MJ, Armitage NM, Farrands PA, Hardcastle JD, Perkins A (1983) Monoclonal antibody 791T/36 for tumor detection and therapy of metastases. In: Nicholson GL, Milas L (eds) Cancer invasion and metastasis, 36th Annual M. D. Anderson Symposium on Fundamental Cancer Research (in press)

  8. Berche C, Mach J-P, Lumbroso J-D, Langlais C, Aubry F, Buchegger F, Carrel S, Rougier P, Parmentier C, Tubiana M (1982) Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: first clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen. Br Med J 285:1147

    Google Scholar 

  9. Brooks CG, Flannery FR (1980) Quantitative studies of natural immunity to solid tumours in rats. Persistence of natural immunity throughout reproductive life and absence of suppressor cells in infant rats. Immunology 39:187

    Google Scholar 

  10. Carlsson J, Drevin H, Axen R (1978) Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio) propionate. A new heterobifunctional reagent. Biochem J 173:723

    Google Scholar 

  11. Embleton MJ, Gunn B, Byers VS, Baldwin RW (1981) Anti-tumour reactions of monoclonal antibody against a human osteogenic sarcoma cell line. Br J Cancer 43:582

    Google Scholar 

  12. Embleton MJ, Rowland GF, Simmonds RG, Jacobs E, Marsden CH, Baldwin RW (1983) Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate. Br J Cancer 47:43

    Google Scholar 

  13. Epenetos AA, Mather S, Gronowska M, Nimmon CC, Hawkins LR, Britton KE, Shepherd J, Taylor-Papadimitriou J, Durbin H, Malpas JS, Bodmer WF (1982) Targeting of iodine-123-labelled tumour-associated monoclonal antibodies to ovarian, breast and gastrointestinal tumours. Lancet II:999

    Google Scholar 

  14. Farrands PA, Perkins AC, Pimm MV, Embleton MJ, Hardy JD, Baldwin RW, Hardcastle JD (1982) Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody. Lancet II:397

    Google Scholar 

  15. Farrands PA, Perkins A, Sully L, Hopkins JS, Pimm MV, Baldwin RW, Hardcastle JD (1983) Localisation of human osteosarcoma by antitumour monoclonal antibody (791T/36). J Bone Joint Surg [Br] (in press)

  16. Fidler IJ, Poste G (1982) Macrophage-mediated destruction of malignant tumor cells and new strategies for the therapy of metastatic disease. In: Baldwin RW, Miescher PA, Muller-Eberhard HJ (eds) Springer Seminars in immunopathology, vol 5. Springer, New York pp 161–174

    Google Scholar 

  17. Garnett MC, Embleton MJ, Jacobs E, Baldwin RW (1983) Preparation and properties of a drug carrier-antibody conjugate showing selective antibody directed cytoxicity in vitro. Int J Cancer 31:661

    Google Scholar 

  18. Golub SH, Dorey F, Hara D, Morton DL, Burk MW (1982) Systemic administration of human leukocyte interferon to melanoma patients. I. Effects on natural killer function and cell populations. J Natl Cancer Inst 68:703

    Google Scholar 

  19. Herberman RB, Ortaldo JR, Mantovani A, Hobbs DS, Kung H, Pestka S (1982) Effect of human recombinant interferon on cytotoxic activity of natural killer (NK) cells and monocytes. Cell Immunol 67:160

    Google Scholar 

  20. Key ME, Talmadge JE, Fogler WE, Bucana C, Fidler IJ (1982) Isolation of tumoricidal macrophages from lung melanoma metastases of mice treated systemically with liposomes containing a lipophilic derivative of muramyl dipeptide. J Natl Cancer Inst 69:1189

    Google Scholar 

  21. Krolick KA, Uhr J, Slavin S, Vitetta ES (1982) In vivo therapy of a murine B cell tumor (BCL1) using antibody-ricin A chain immunotoxins. J Exp Med 155:1797

    Google Scholar 

  22. Lang NP, Ortaldo JR, Bonnard GD, Herberman RB (1982) Interferon and prostaglandins: effects on human natural and lectin-induced cytotoxicity. J Natl Cancer Inst 69:339

    Google Scholar 

  23. Moller G (ed) (1982) Antibody carriers of drugs and toxins in tumour therapy. Immunol Rev 62:1–216

  24. Ortaldo JR, Lang NP, Timonen T, Herberman RB (1981) Augmentation of human natural killer cell activity by interferon: Conditions required for boosting and characteristics of the effector cells. J Interferon Res 1:253

    Google Scholar 

  25. Pattengale PK, Gidlund M, Nilsson K, Sundström C, Sallström I, Simonsson B, Wigzell H (1982) Lysis of fresh human B-lymphocyte-derived leukemia cells by interferon-activated natural killer (NK) cells. Int J Cancer 29:1

    Google Scholar 

  26. Pimm MV, Embleton MJ, Perkins AC, Price MR, Robins RA, Robinson GR, Baldwin RW (1982) In vivo localization of anti-osteogenic sarcoma 791T monoclonal antibody in osteogenic sarcoma xenografts. Int J Cancer 30:75

    Google Scholar 

  27. Robins RA, Baldwin RW (1983) Role of T-lymphocyte susbsets in tumor rejection: implications for developing biological response modifying and monitoring tumor-host interactions during tumor development. Journal of Biological Response Modifers 2:101

    Google Scholar 

  28. Rowland GF, Simmonds RG, Corvalan JRF, Baldwin RW, Brown JP, Embleton MJ, Ford CHJ, Hellström KE, Hellström I, Kemshead JT, Newmann CE, Woudhouse CS (1982) Monoclonal antibodies for targeted therapy with vindesine. In: Peeters H (ed) Protides of the biological fluids. Pergamon Press, London, pp 375–379

    Google Scholar 

  29. Steel GG, Courtney VD, Rostom AY (1978) Improved immune suppression technique for the xenografting of human tumours. Br J Cancer 37:224

    Google Scholar 

  30. Willmott N, Austin EB, Pimm MV, Baldwin RW (1981) Evaluation of intratumoral immunostimulants in the treatment of a transplantable rat mammary carcinoma. Eur J Cancer 17:397

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Research Campaign Laboratories, University of Nottingham, Nottingham, England

    Julie M. Pelham, J. D. Gray, G. R. Flannery, M. V. Pimm & R. W. Baldwin

Authors
  1. Julie M. Pelham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. D. Gray
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. R. Flannery
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. V. Pimm
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. W. Baldwin
    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

Pelham, J.M., Gray, J.D., Flannery, G.R. et al. Interferon-α conjugation to human osteogenic sarcoma monoclonal antibody 791T/36. Cancer Immunol Immunother 15, 210–216 (1983). https://doi.org/10.1007/BF00199167

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00199167

Keywords

Search

Navigation