Skip to main content

Advertisement

SpringerLink
Log in

The Potential Role of Immunoconjugates in Targeting Cytotoxic Agents To Brain Tumours

  • Leading Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Summary

Advances in surgical, radiation and chemotherapeutic techniques for the treatment of tumours of the CNS have not improved the prognosis of this type of cancer. Furthermore, the CNS represents a unique challenge to traditional chemotherapy because of the blood-brain barrier, the variety of tumours present within the CNS and heterogeneity within a given tumour type. Monoclonal antibody technology has provided a variety of new agents to explore as possible therapies for cancers. The use of antibodies to target isotopes, toxins, drugs or enzymes to brain tumours is currently being investigated.

A number of phenomena may affect the ability of these immunoconjugates to reach the target and their efficacy once at the target site. These include tumour susceptibility and accessibility, target antigen expression, the immune response of the patient and tumour heterogeneity. We conclude, based on our research and that of others, that immunoconjugates are effective against compartmentalised tumours in the CNS, and their primary role may be in the treatment of residual disease or in combined therapeutic regimens.

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. Black PM. Brain tumours. N Engl J Med 1991; 324: 1471–6

    Article  PubMed  CAS  Google Scholar 

  2. Black PM. Brain tumours. N Engl J Med 1991; 324: 1555–64

    Article  PubMed  CAS  Google Scholar 

  3. Pizzo PA, Horowitz ME, Poplak DG, et al. Solid tumours in childhood. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer principles and practice of oncology. Philadelphia: JB Lippincott, 1992: 1738–91

    Google Scholar 

  4. Blakey DC. Drug targeting with monoclonal antibodies: a review. Rev Oncology 1992; 5: 91–7

    Google Scholar 

  5. Byers VS, Baldwin RW. Therapeutic strategies with monoclonal antibodies and immunoconjugates. Immunology 1988; 65: 329–35

    PubMed  CAS  Google Scholar 

  6. Frankel AE. Immunotoxin therapy of cancer. Oncology 1993; 7: 70–8

    Google Scholar 

  7. Eiklid K, Olsnes S, Pihl A. Entry of lethal doses of abrin, ricin, and modeccin into the cytosol of HeLa cells. Exp Cell Res 1980; 126: 321–6

    Article  PubMed  CAS  Google Scholar 

  8. Bagshawe KD, Springer CJ, Searle F, et al. A cytotoxic agent can be generated at cancer sites. Br J Cancer 1988; 58: 700–3

    Article  PubMed  CAS  Google Scholar 

  9. Johnson VG, Wrobel C, Wilson D, et al. Improved tumor specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia. J Neurosurg 1989; 70: 240–8

    Article  PubMed  CAS  Google Scholar 

  10. Pietersz GA, McKenzie IFC. Antibody conjugates for the treatment of cancer. Immunol Rev 1992; 129: 57–80

    Article  PubMed  CAS  Google Scholar 

  11. Goldenberg DM. Monoclonal antibodies in cancer detection and therapy. Am J Med 1993; 94: 297–312

    Article  PubMed  CAS  Google Scholar 

  12. Kemshead JT, Papanastassiou V, Coakham HB, et al. Monoclonal antibodies in the treatment of central nervous system malignancies. Eur J Cancer 1992; 28: 511–3

    Article  PubMed  CAS  Google Scholar 

  13. Jones PT, Dear PH, Foote J, et al. Replacing the complimentarity-determining regions in a human antibody with those from the mouse. Nature 1986; 321: 522–5

    Article  PubMed  CAS  Google Scholar 

  14. Oi VT, Morrison SL. Chimeric antibodies. Biotechniques 1986; 4: 214–21

    CAS  Google Scholar 

  15. Reichmann L, Clark MR, Walmann H, et al. Reshaping antibodies for therapy. Nature 1988; 332: 323–7

    Article  Google Scholar 

  16. Neuwelt EA, Balaban E, Diehl J, et al. Successful treatment of primary central nervous system lymphomas with chemotherapy after osmotic blood-brain barrier opening. Neurosurgery 1983; 12: 662–71

    Article  PubMed  CAS  Google Scholar 

  17. White S, Taetle R, Seligman PA, et al. Combinations of anti-transferrin receptor monoclonal antibodies inhibit tumor cell growth in vitro and in vivo: evidence of synergistic anti-proliferative effects. Cancer Res 1990; 50: 6295–301

    PubMed  CAS  Google Scholar 

  18. Lashford LS, Davies AG, Richardson RB, et al. A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors. Cancer 1988; 61: 857–68

    Article  PubMed  CAS  Google Scholar 

  19. Donelli MG, Zucchetti M, D’Incalci M. Do anticancer agents reach the tumor-target in the human brain? Cancer Chemother Pharmacol 1992; 30: 251–60

    Article  PubMed  CAS  Google Scholar 

  20. Zhu JH, Du Zw, Huang Q, et al. Drug-targeting by monoclonal antibody in neuro-oncology [abstract]. Childs Nerv Syst 1990; 6: 309

    Google Scholar 

  21. Papanastassiou V, Pizer BL, Coakham HB, et al. Treatment of recurrent and cystic malignant gliomas by a single intracavity injection of 131I monoclonal antibody: feasibility, pharmacokinetics and dosimetry. Br J Cancer 1993; 67: 144–51

    Article  PubMed  CAS  Google Scholar 

  22. Muraszko KM, Sung C, Walbridge, et al. Pharmacokinetics and toxicology of immunotoxins administered into the subarachnoid space in nonhuman primates and rodents. Cancer Res 1993; 53: 3752–7

    PubMed  CAS  Google Scholar 

  23. Moseley RP, Davies AG, Richardson RB, et al. Intrathecal administration of 131I radiolabelled monoclonal antibody as a treatment of neoplastic meningitis. Br J Cancer 1990; 62: 637–42

    Article  PubMed  CAS  Google Scholar 

  24. Zovickian JG, Johnson VG, Youle RJ. Potent and specific killing of human malignant brain tumor cells by an anti-transferrin receptor antibody-ricin immunotoxin. J Neurosurg 1987; 66: 850–61

    Article  PubMed  CAS  Google Scholar 

  25. Hall WA, Fodstad O. Immunotoxins and central nervous system neoplasia. J Neurosurg 1992; 76: 1–12

    Article  PubMed  CAS  Google Scholar 

  26. Colombatti M, Bisconti M, Dell’Arciprete MA, et al. Sensitivity of human glioma cells to cytotoxic heteroconjugates. Int J Cancer 1988; 42: 441–8

    Article  PubMed  CAS  Google Scholar 

  27. Recht LD, Griffin TW, Raso V, et al. Potent cytotoxicity of an antihuman transferrin receptor-ricin A chain immunotoxin on human glioma cells in vitro. Cancer Res 1990; 50: 6696–700

    PubMed  CAS  Google Scholar 

  28. Recht L, Torres CO, Smith TW, et al. Transferrin receptor in normal and neoplastic brain tissue: implications for brain tumor immunotherapy. J Neurosurg 1990; 72: 941–5

    Article  PubMed  CAS  Google Scholar 

  29. Martell LA, Agrawal A, Ross DA, et al. Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors. Cancer Res 1993; 53: 1348–53

    PubMed  CAS  Google Scholar 

  30. Zovickian JG, Youle RJ. Efficacy of intrathecal immunotoxin therapy in an animal model of leptomeningeal neoplasia. J Neurosurg 1988; 68: 767–74

    Article  PubMed  CAS  Google Scholar 

  31. Urch CE, George AJT, Stevenson GT, et al. Intra-thecal treatment of leptomeningeal lymphoma with immunotoxin. Int J Cancer 1991; 47: 909–15

    Article  PubMed  CAS  Google Scholar 

  32. Reidel CJ, Muraszko KM, Youle RJ. Diphtheria toxin mutant selectively kills cerebellar Purkinje neurons. Proc Natl Acad Sci USA 1990; 87: 5051–5

    Article  Google Scholar 

  33. Fuchs HE, Archer GE, Colvin OM, et al. Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis. Cancer Res 1990; 50: 1954–9

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Brain Tumor Research Laboratory, Department of Surgery, Section of Neurosurgery, The University of Michigan Medical Center, Ann Arbor, Michigan, USA

    Lori A. Martell & Karin M. Muraszko

Authors
  1. Lori A. Martell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karin M. Muraszko
    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

Martell, L.A., Muraszko, K.M. The Potential Role of Immunoconjugates in Targeting Cytotoxic Agents To Brain Tumours. CNS Drugs 2, 175–183 (1994). https://doi.org/10.2165/00023210-199402030-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199402030-00001

Keywords

Search

Navigation