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Antitumor monoclonal antibodies for radioimmunodetection of tumors and drug targeting

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Summary

Developments in hybridoma technology leading to the production of monoclonal antibodies recognizing tumor-associated antigens are providing new approaches for the radioimmunodetection of, and drug targeting to, metastases. These developments are illustrated in a series of studies on the in vivo localization of an antihuman-osteogenic sarcoma monoclonal antibody (791T/36) in human tumor xenografts maintained in immunodeprived mice. 131I-labelled 791T/36 antibody localized specifically in osteogenic sarcomas but not in xenografts of other tumors, such as bladder carcinoma T24, which do not express the antigen identified by this antibody. Developing from these studies, various parameters influencing antibody localization in tumors were examined including the kinetics of antibody uptake, the relationshiop between tumor size and antibody binding, and the site of antibody deposition. This provides a basis for considering the potential of antitumor monoclonal antibodies for targeting antitumor agents. Of particular importance here is the observation that antibody is principally located at the periphery of tumors since this will influence the population of cells within a tumor which can be attacked by antibody-drug or antibody-toxin conjugates.

Experiments with human tumor xenografts demonstrate tumor localization of radioisotope-labelled 791T/36 monoclonal antibody. Tumor localization by external gamma camera imaging of osteogenic sarcoma xenograft-bearing mice was also demonstrated. These studies illustrate the potential of antitumor monoclonal antibodies for imaging primary and metastatic tumors. This approach is further emphasized by the radioimmunodetection of primary and metastatic colorectal carcinomas.

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References

  1. Stella VJ, Himmelstein KJ: Pro drugs and site-specific drug delivery. J Med Chem (23): 1275–1283, 1980.

    Google Scholar 

  2. Widder KJ, Senyei AE, Sears B: Experimental methods in cancer therapeutics. J Pharmaceut Sci (71): 379–387, 1982.

    Google Scholar 

  3. Fidler IJ, Poste G: Macrophage-mediated destruction of malignant tumor cells and new strategies for the therapy of metastatic disease. Springer Semin Immunopathol (5): 161–174, 1982.

    Google Scholar 

  4. Baldwin RW, Byers VS: Immunoregulation by bacterial organisms and their role in the immunotherapy of cancer. Springer Semin Immunopathol (2): 79–100, 1979.

    Google Scholar 

  5. Lederer E: Immunostimulation: recent progress in the study of natural and synthetic immunomodulators derived from the bacterial cell wall. In: Fougereau M, Dausset J (eds) Immunology 80: progress in immunology, Vol 4. London, Academic Press, 1980, pp 1194–1211.

    Google Scholar 

  6. Berthold W, Masucci MG, Klein E, Strander H: Interferon treatment elevates the cytotoxic potential of lymphocytes and thereby increases the frequency of functional killer cells. Human Lymph Diff (1): 1–12, 1981.

    Google Scholar 

  7. Pimm MV, Hopper DG, Baldwin RW: BCG treatment of malignant pleural effusions in the rat. Br J Cancer (34): 368–373, 1976.

    Google Scholar 

  8. Sone S, Fidler IJ: In situ activation of tumoricidal properties in rat alveolar macrophages and rejection of experimental lung metastases by intravenous injections of Nocardia rubra cell wall skeleton. Cancer Immunol Immunother (12): 203–209, 1982.

    Google Scholar 

  9. Arnon R: Anti-tumor antibodies as carriers for anti-cancer drugs. In: Spreafico F, Arnon R (eds) Tumor-associated antigens and their specific immune response. London, Academic Press, 1979, pp 287–304.

    Google Scholar 

  10. Baldwin RW, Embleton MJ, Price MR: Monoclonal antibodies specifying tumour associated antigens and their potential for therapy. Molec Aspects Med (4): 329–368, 1981.

    Google Scholar 

  11. Hellström KE, Hellström I, Brown JP: Human tumor-associated antigens identified by monoclonal antibodies. Springer Semin Immunopathol (5): 127–146, 1982.

    Google Scholar 

  12. Gilliland DG, Steplewski Z, Collier RJ, Mitchell KF, Chang TH, Koprowski H: Antibody directed cytotoxic agents: use of monoclonal antibody to direct the reaction of toxin A chains to colorectal carcinoma cells. Proc Natl Acad Sci USA (77): 4539–4543, 1980.

    Google Scholar 

  13. Thorpe PE, Ross WCJ: The preparation and cytotoxic properties of antibody toxin conjugates. Immunol Rev (62): 119–158, 1982.

    Google Scholar 

  14. Krolik KA, Yuan D, Vitetta ES: Specific killing of a human breast carcinoma cell line by a monoclonal antibody coupled to the A-chain of Ricin. Cancer Immunol Immunother (12): 39–41, 1981.

    Google Scholar 

  15. Pimm MV, Jones JA, Price MR, Middle JG, Embleton MJ, Baldwin RW: Tumour localization of monoclonal antibody against a rat mammary carcinoma and suppression of tumour growth with adriamycin-antibody conjugates. Cancer Immunol Immunother (12): 125–134, 1982.

    Google Scholar 

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

  17. Baldwin RW, Flannery GB, Pelham JM, Dixon-Gray J: Immunomodulation by IFN-conjugated monoclonal antibody to human osteogenic sarcoma. Proc Am Assoc Cancer Res (23): 254, 1982 (abstract).

    Google Scholar 

  18. Pimm MV, Embleton MJ, Perkins AC, Price MR, Robins RA, Robinson GR, Baldwin RW: In vivo localization of anti-osteogenic sarcoma 791T monoclonal antibody in osteogenic sarcoma xenografts. Int J Cancer (30): 75–85, 1982.

    Google Scholar 

  19. Price MR, Pimm MV, Dawood FA, Embleton MJ, Baldwin RW: Characteristics and tumour localizing properties of anti-human osteogenic sarcoma monoclonal antibodies. In: Lapis K, Jeney A (eds) Tumor progression and markers. Amsterdam, Kugler Press, 1982.

    Google Scholar 

  20. Hellström I, Brown JP, Hellström KE: Monoclonal antibodies to two determinants of melanoma-antigen p97 act synergistically in complement-dependent cytotoxicity. J Immunol (127): 157–160, 1981.

    Google Scholar 

  21. Mach JP, Buchegger F, Forni M, Ritschard J, Berche C, Lumbroso J-D, Schreyer M, Girardet C, Allolla RS, Carrel S: Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy. Immunol Today (2): 239–249, 1981.

    Google Scholar 

  22. Moshakis V, Bailey MJ, Ormerod MG, Westwood JH, Neville AM: Localization of human breast carcinoma xenografts using antibodies to carcino-embryonic antigen. Br J Cancer (43): 575–581, 1981.

    Google Scholar 

  23. Moshakis V, McIlhinney RAJ, Raghavan D, Neville AM: Localization of human tumour xenografts after i.v. administration of radiolabelled monoclonal antibodies. Br J Cancer (44): 91–99, 1981.

    Google Scholar 

  24. Warenius HM, Galfre G, Bleehen NM, Milstein C: Attempted targeting of a monoclonal antibody in a human tumour xenograft system. Eur J Cancer (17): 1009–1015, 1981.

    Google Scholar 

  25. Price MR, Baldwin RW: Shedding of tumour cell surface antigens. In: Poste G, Nicholoson GL (eds) Dynamic aspects of cell surface organisation. Amsterdam, Elsevier/North-Holland, 1977, pp 423–471.

    Google Scholar 

  26. Sundquist KG: Dynamics of antibody binding and complement interactions at the cell surface. In: Poste G, Nicholson GL (eds) Dynamic aspects of cell surface organisation. Amsterdam, Elsevier/North-Holland, 1977, pp 551–600.

    Google Scholar 

  27. Epenetos AA, Nimmon CC, Arklie J, Elliott AT, Hawkins LA, Knowles RW, Britton KE, Bodmer WF: Detection of human cancer in an animal model using radiolabelled tumour-associated monoclonal antibodies. Br J Cancer (46): 1–8, 1982.

    Google Scholar 

  28. Moshakis V, McIlhinney RAJ, Neville AM: Cellular distribution in human tumours after i.v. administration. Br J Cancer (44): 663–669 1981.

    Google Scholar 

  29. Moshakis V, McIlhinney RAJ, Raghavan D, Neville AM: Monoclonal antibodies to detect human tumours: an experimental approach. J Clin Pathol (34): 314–319, 1981.

    Google Scholar 

  30. Moshakis V, Ormerod MG, Westwood JH, Imrie S, Neville AM: The site of binding of anti-CEA antibodies to tumour CEA in vivo: an immunocytochemical and autoradiographic approach. Br J Cancer (46): 18–21, 1982.

    Google Scholar 

  31. Eckelman WC, Paik CH, Reba RC: Radiolabelling of antibodies. Cancer Res (40): 3036–3042, 1980.

    Google Scholar 

  32. Goldenberg DM, Deland F, Kim E, Bennett S, Primus FJ, Nagel JR, Estes N, Desimone P, Rayburn P: Use of radiolabelled antibodies to carcinoembryonic antigen for the detection of localization of diverse cancers by external photoscanning. N Engl J Med (298): 1384–1388, 1978.

    Google Scholar 

  33. Layne WW, Hnatowich DJ, Doherty PW, Childs RL, Lanteigne D, Ansell J: Evaluation of the viability of In-111-labelled DTPA coupled to fibrinogen. J Nucl Med (23): 627–630, 1982.

    Google Scholar 

  34. Khaw BA, Fallon JT, Strauss HW, Haber E: Myocardial infarct imaging of antibodies to canine cardiac myosin with Indium-111 diethylenetriamine pentaacetic acid. Science (209): 295–297, 1980.

    Google Scholar 

  35. Halpern SE, Hagan PL, Garver PR: Comparison of In-111 anti-CEA monoclonal antibodies (MoAb) and endogenously labelled Se-75 MoAbs in normal and tumour bearing mice. J Nucl Med (23): 8, 1982.

    Google Scholar 

  36. DeLand FH, Kim EE, Simmons G, Goldenberg DM: Imaging approach to radioimmunodetection. Cancer Res (40): 3046–3049, 1980.

    Google Scholar 

  37. Perkins AC, Hardy JG, Whalley DR, Pimm MV, Farrands PA: Image enhancement in immunoscintigraphy. Nucl Med Comm (3): 122, 1982.

    Google Scholar 

  38. Farrands PA, Perkins AC, Pimm MV, Embleton MJ, Hardy JD, Baldwin RW, Hardcastle JD: Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody. Lancet (II): 397–400, 1982.

    Google Scholar 

  39. Ballou B, Levine G, Hakala TR, Solter D: Tumour location detected with radioactively labelled monoclonal antibody and external scintigraphy. Science (206): 844–847, 1979.

    Google Scholar 

  40. Rockoff SD, Goodenough DJ, McIntire KR: Theorectical limitations in the immunodiagnostic imaging of cancer with computed tomography and nuclear scanning. Cancer Res (40): 3054–3058, 1980.

    Google Scholar 

  41. Ashall F, Bramwell ME, Harris H: A new marker for human cancer cells. 1. The Ca antigen and the Cal antibody. Lancet (II): 1–6, 1982.

    Google Scholar 

  42. McGee JO'D, Woods Julie C, Ashall F, Bramwell ME, Harris H: A new marker for human cancer cells. 2. Immunohistochemical detection of the Ca antigen in human tissues with the Cal antibody. Lancet (II): 7–10, 1982.

    Google Scholar 

  43. Gaffar SA, Bennett SJ, DeLand FH, Primus FJ, Goldenberg DM: Carcinoembryonic antigen (CEA) radioactive antibody fragments for cancer localization in vivo. (Abstract) Proc Am Assoc Cancer Res (23): 249, 1982.

    Google Scholar 

  44. Sears HF, Atkinson B, Mattis J, Ernst C Herlyn D, Steplewski Z, Hayry P, Koprowski H: Phase-1 Clinical trial of monoclonal antibody in treatment of gastrointestinal tumours. Lancet (I): 762–765, 1982.

    Google Scholar 

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

    Robert W. Baldwin & Malcolm V. Pimm

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  1. Robert W. Baldwin
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  2. Malcolm V. Pimm
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Baldwin, R.W., Pimm, M.V. Antitumor monoclonal antibodies for radioimmunodetection of tumors and drug targeting. Cancer Metast Rev 2, 89–106 (1983). https://doi.org/10.1007/BF00046907

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