Monoclonal Antibodies as Targeting Agents for Cytotoxic Compounds In Vivo: A Current Assessment

  • J. T. Kemshead
  • D. H. Jones
  • L. Lashford
  • J. Pritchard
  • I. Gordon
  • F. Breatnach
  • H. B. Coakham
Conference paper
Part of the Progress in Pediatric Surgery book series (PEDIATRIC, volume 22)


The idea of antibodies acting as magic bullets to target cytotoxic compounds selectively to specific sites in the body was introduced by Hericourt and Richet in 1895 [10] and Ehrlich in 1913 [7]. The use of hetero-antisera as a targeting medium has however, in many cases, been fraught with problems. These include difficulties in absorbing reagents to obtain sera of high specificity, and the irreproducibility of batches of antisera prepared in different animals [3, 13]. Despite this, several workers have successfully used radiolabelled polyclonal antisera for scintigraphic studies in patients with a variety of malignancies [2, 8, 16]. In addition, Order and Lenhard have used radiolabelled hetero-antisera to treat hepatocellular carcinoma and Hodgkin’s disease [15, 20]. To avoid the problem of host antibody responses changing the pharmacokinetics of the targeting agent, they used antibodies prepared in a variety of different species.


Target Agent Cytotoxic Compound Target Radiation Therapy Irrelevant Antibody Radiolabelled Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allan PM, Garson JA, Harper EI, Asser U, Coakham HB, Brownell B, Kemshead JT (1983) Biological characterisation and clinical applications of a monoclonal antibody recognising an antigen restricted to neuroectodermal tissues. Int J Cancer 31:591–598PubMedCrossRefGoogle Scholar
  2. 2.
    Begent RHJ, Searle F, Stanway G, Jewkes RF, Jones BE, Vernon P, Bagshawe KD (1980) Radioimmunolocalisation of tumours by external scintigraphy after administration of 131I antibody to human chorionic gonadotrophin: preliminary communication. J R Soc Med 73:624–630PubMedGoogle Scholar
  3. 3.
    Casper JT, Borella L, Sen L (1977) Reactivity of human brain antiserum with neuroblastoma cells and non-reactivity with thymocytes and lymphoblasts. Cancer Res 37:1750–1756PubMedGoogle Scholar
  4. 4.
    Coakham HB, Richardson RB, Bourne SB, Davies AG, Kemshead JT (1985) Antibody guided radioimmunolocalisation and therapy for malignant meningitis. Br J Cancer 52:655Google Scholar
  5. 5.
    Epenetos AA, Courtnay-Luck N, Hainan KE, Hooker G, Hughes JMB, Krauss D, Lambert J, Lavender JP, MacGregor WG, McKenzie CJ, Munroe A, Myers MJ, Orr JS, Pearse EE, Snook D, Webb B, Burchell J, Durbin H, Kemshead JT, Taylor-Papadimitriou J (1984) Antibody-guided irradiation of malignant lesions: Three cases illustrating a new method of treatment. Lancet 1:1441–1443Google Scholar
  6. 6.
    Epenetos AA, Courtnay-Luck N, Pickering D, et al (1985) Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen. Br J Cancer 290:1463–1466Google Scholar
  7. 7.
    Ehrlich P (1913) Chemotherapy. In: Himmelweit F (ed)( (1960) The collected papers of Paul Ehrlich, vol 3. Pergamon, Oxford, p 510Google Scholar
  8. 8.
    Goldenberg DM, Kim EE, Deland FH (1981) Human chorinoic gonadotropin radioantibodies in the radioimmunodetection of cancer and for disclosure of occult metastases. Proc Natl Acad Sci USA 78:7754–7758PubMedCrossRefGoogle Scholar
  9. 9.
    Goldman A, Vivian G, Gordon I, Pritchard J, Kemshead JT (1984) Immunolocalisation of neuroblastoma using radiolabelled monoclonal antibody UJ13A. J Paediatr 105:252–256CrossRefGoogle Scholar
  10. 10.
    Héricourt J, Richet C (1895) Traitement d’un cas de sarcome par la sérothérapie. CR Hebd Seances Acad Sci 120:948–950Google Scholar
  11. 11.
    Jones DH, Goldman A, Gordon I, Pritchard J, Gregory BJ, Kemshead JT (1985) Therapeutic application of a radiolabelled monoclonal antibody in nude mice xenografted with human neuroblastoma: Tumoricidal effects and distribution studies. Int J Cancer 35:715–720PubMedCrossRefGoogle Scholar
  12. 12.
    Kemshead JT, Greaves MF, Pritchard J, Graham-Pole J (1980) Differential expression of surface antigens on human neuroblastoma cells. In: Evans AE (ed) Advances in neuroblastoma research. Academic, New York, pp 227–235Google Scholar
  13. 13.
    Kemshead JT, Goldman A, Jones D, Pritchard J, Malpas JS, Gordon I, Malone JF, Hurley GD, Breatnach F (1985) Therapeutic application of radiolabeled UJ13A in children with disseminated neuroblastoma — a phase 1 study. In: Evans AE, D’Angio GJ, Seeger RC (eds) Advances in Neuroblastoma research. Liss, New York, pp 533–544Google Scholar
  14. 14.
    Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRefGoogle Scholar
  15. 15.
    Lenhard RE, Order SE, Spunberg JJ, Ettinger DS, Askell SO, Leibel SA (1983) Radioimmunoglobulins: A new therapeutic modality in Hodgkin’s disease. Am Soc Clin Oncol, abstract, 825 211Google Scholar
  16. 16.
    Mach JP, Carrell S, Forni M (1980) Tumour localisation of radiolabelled antibodies against carcioembryonic antigen in patients with carcinoma. New Engl J Med 303:5–10PubMedCrossRefGoogle Scholar
  17. 17.
    Mach JP, Bucheggar F, Forni M, Ritschard J, Berche C, Lumbroso JD, Sehreyer M, Giradet C, Accolla RS, Carrel S (1981) Use of a radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy. Immunol Today 2:239–249CrossRefGoogle Scholar
  18. 18.
    Miller RA, Maloney DG, Warnke R, Levy R (1982) Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. New Engl J Med 306:517–523PubMedCrossRefGoogle Scholar
  19. 19.
    Moldofsky PJ, Powe J, Mulhern CB, Hammond N, Sears HF, Gatenby RA, Steplewski Z, Koprowski H (1983) Metastatic colon carcinoma detected with radiolabeled F(ab)2 monoclonal antibody fragments. Radiology 149(2):549–555PubMedGoogle Scholar
  20. 20.
    Order SE, Ettinger DS, Leibel SA, Klein JL, Leichner PK (1983) Cyclic radiolabelled 131I anti-ferritin in multimodality therapy of hepatocellular carcinoma. Am Soc Clin Oncol, abstract, 463 119Google Scholar
  21. 21.
    Pallensen G, Jepsen FL, Hastrup J, Ipsen A, Hvidberg N (1983) Experience with the Oxford tumour marker (Cal) in serous fluids. Lancet 1:1326CrossRefGoogle Scholar
  22. 22.
    Philip D, Biron P, Philip I, Favrot M, Bernard JL, Zucker JM, Lutz B, Plouvier E, Rebattau P, Carton M, Chauvot P, Dutou L, Souillet G, Phillippe N, Boridigoni P, Lacroze M, Clapisson G, Olive D, Treleaven J, Kemshead JT (1985) Autologous bone marrow transplantation for very bad prognosis neuroblastoma. In: Evans AE, D’Angio GJ, Seeger RC (eds) Advances in neuroblastoma research. Liss, New York, pp 568–586Google Scholar
  23. 23.
    Richardson RB, Davies AG, Bourne S, Stadden F, Kemshead JT, Coakham HB (1987) Radioimmunolocalisation of brain tumours. I. Scintigraphic studies. J NeuroncolGoogle Scholar
  24. 24.
    Rowland GF, Simmonds RG, Corvalan JRF, Baldwin RW, Brown JP, Embleton MJ, Ford CHJ, Hellstrom KE, Hellstrom I, Kemshead JT, Newman CE, Woodhouse CS (1982) Monoclonal antibodies for targetted therapy with vindesine. Protides Biol Fluids 30:375–379Google Scholar
  25. 25.
    Schnegg JF, Diserens AC, Carrell S, Accolla RS, deTribolet N (1981) Human glioma-associated antigens detected by monoclonal antibodies. Cancer Res 41:1209–1213PubMedGoogle Scholar
  26. 26.
    Shafford EA, Rogers DW, Pritchard J (1985) Improved response rate using multiagent regimen (OPEC) including sequential cisplatinum and VM26. J Clin Oncol 2:742–747Google Scholar
  27. 27.
    Silvermann CL, Palks H, Tatent B, Kovnar E, Clouse JW, Thomas RN (1984) Late effect of radiation in patients with cerebellar medulloblastoma. Cancer 54:825–829CrossRefGoogle Scholar
  28. 28.
    Taylor CH, Morley TP, Olszewski J (1965) A study of the factors responsible for the accumulation of radioactive iodinated human serum albumin (RIHSA) by intracranial tumour and other lesions. J Neurosurg 22:60–76CrossRefGoogle Scholar
  29. 29.
    Taylor-Papadimitriou J, Peterson JA, Arklie J, Burchell J, Ceriani RC, Bodmer WF (1981) Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane, colon production and reaction with cells in culture. Int J Cancer 28:17–21PubMedCrossRefGoogle Scholar
  30. 30.
    Thorpe PE, Ross WCJ (1982) The preparation and cytotoxic properties of antibody toxin conjugates. Immunol Rev 62:119–158PubMedCrossRefGoogle Scholar
  31. 31.
    Tso MDM, Shih CY (1976) Disruption of blood retinal barrier in ocular hypotony: preliminary report. Exp Eye Res 23:209–216PubMedCrossRefGoogle Scholar
  32. 32.
    Vick Na, Bigner DD (1972) Microvascular metastasis abnormalities in virally induced canine brain tumours: structural basis from altered blood brain barrier function. J Neurol Sci 17:29–39PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • J. T. Kemshead
    • 1
  • D. H. Jones
    • 1
  • L. Lashford
    • 1
  • J. Pritchard
    • 2
  • I. Gordon
    • 3
  • F. Breatnach
    • 4
  • H. B. Coakham
    • 5
  1. 1.ICRF Oncology LaboratoriesInstitute of Child HealthLondonUK
  2. 2.Department of Haematology and OncologyThe Hospital for Sick ChildrenLondonUK
  3. 3.Department of Radiology and Nuclear MedicineThe Hospital for Sick ChildrenLondonUK
  4. 4.Our Lady’s Hospital for Sick ChildrenCrumlin, DublinIreland
  5. 5.Department of NeurosurgeryFrenchay HospitalBristolUK

Personalised recommendations