Recent Perspectives on the Use of Radiolabeled Monoclonal Antibodies for Immunotherapy

  • Rashid A. Fawwaz
  • Theodore S. T. Wang
  • Suresh C. Srivastava
  • Rodney Bigler
  • Mark Hardy
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 152)


Recent advances in hybridoma technology have led to the development of specific monoclonal antibodies to a variety of tumor-associated antigens. The high degree of specificity of such reagents has rekindled interest in their application to immunotherapy of malignancies. In-vitro culture studies and experiments in various in-vivo animal models have usually shown that monoclonal antibodies, even in the presence of complement, are rarely alone sufficiently cytotoxic and therefore usually ineffective for tumor destruction (1,2). This ineffectiveness of monoclonal antibodies when used in unmodified forms has been partially attributed to the heterologous distribution of tumor-associated antigens on tumor cell surfaces which therefore results in an insufficient attachment of monoclonal antibodies to different tumor cells; more to those cells which have a significant number of binding sites for the antigen but none to other tumor cells that are devoid of binding sites for the specific antigen (3). Thus, while tumor cells which express the specific antigen may under appropriate circumstances undergo lysis, those which are negative for the antigen are spared and continue to proliferate. Monoclonal antibodies directed to tumor-associated antigens which are coupled to various toxins suffer from the same shortcomings that have been described for unmodified antitumor monoclonal antibodies.


Monoclonal Antibody Thyroid Carcinoma Follicular Thyroid Carcinoma Mouse Immunoglobulin Tumor Cell Surface 
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.
    S. T. Rosen, J. Winter, and Epstein, Application of monoclonal antibodies for tumor diagnosis and therapy, Ann. Clin. Lab. Sci. 13:173 (1983).PubMedGoogle Scholar
  2. 2.
    R. A. Miller, A. R. Oseroff, P. Stratke, et al., Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma, Blood 62:988 (1983).PubMedGoogle Scholar
  3. 3.
    A. A. Epenetos, G. Canti, R. Taylor, et al., Use of two epithelium specific monoclonal antibodies for diagnosis of malignancy in serous effusions, Lancet ii:1000 (1982).Google Scholar
  4. 4.
    W. H. Beierwaltes, R. H. Nishiyana, N. W. Thompson, et al., Survival time and cure in papillary and follicular thyroid carcinoma with distant metastases, J. Nucl. Med. 23:561 (1982).PubMedGoogle Scholar
  5. 5.
    S. Hochschwender, R. Bartholomew, N. Sanchez, et al., Immunoreactivity of the monoclonal antibody (MAB) 96.5 against the P 97 melanoma associated antigen is directly related to production of inactive variants, J. Nucl. Med. 27:958 (1986).Google Scholar
  6. 6.
    T. S. T. Wang, J. R. Rose, R. Smith, et al., A new approach to bifunctional chelate attachment to antibodies, J. Nuel. Med. 25:56 (1984).Google Scholar
  7. 7.
    T. S. T. Wang, A. K. Ng, R. A. Fawwaz, et al., Heterobifunc-tional reagents. A new approach to radiolabeling of monoclonal antibodies, J. Nucl. Med. 26:46 (1985).Google Scholar
  8. 8.
    D. J. Hnatowich, T. W. Griffin, C. Kosciuczyk, et al., Pharmacokinetics of an Indium-111-labeled monoclonal antibody in cancer patients, J. Nucl. Med. 26:849 (1985).PubMedGoogle Scholar
  9. 9.
    S. J. DeNardo, C. F. Meares, M. K. Moi, Comparative serum stability of Cu-67 and In-111 chelates for diagnosis and therapeutic applications, J. Nucl. Med. 26:P 119 (1985).Google Scholar
  10. 10.
    S. Halpern, The effect of radiolabel on the kinetics of monoclonal anti-CEA in a nude mouse-human colon tumor model, in: “Hybridomas in Cancer Diagnosis and Treatment,” S. Mitchel and H. F. Oettgen, eds., Raven Press, New York (1982).Google Scholar
  11. 11.
    R. M. McCabe, L. C. Peters, M. V. Haspel, et al., Development and Characterization of Human Monoclonal Antibodies and Their Application in the Radioimmunodetection of Colon Carcinoma, This book, Part I.Google Scholar
  12. 12.
    S. Matzku, E. Brocker, J. Brugger, et al., Modes of binding and internalization of monoclonal antibodies to human melanoma cell lines, Can. Res. 46:3848 (1986).Google Scholar
  13. 13.
    P. W. Doherty, D. Hnatowich, R. Childs, et al., Behavior of In-111 labeled F(ab′)2 fragments (19-9) in patients, J Nucl. Med. 25:112 (1984).Google Scholar
  14. 14.
    S. E. Halpern and P. Hagan, Effect of protein mass on the pharmacokinetics of murine monoclonal antibodies, J. Nucl. Med. 26:818 (1985).PubMedGoogle Scholar
  15. 15.
    J. Sutherland, P. Mannoni, F. Rosa, et al., Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate, Hum. Immunol. 12:65 (1985).PubMedCrossRefGoogle Scholar
  16. 16.
    M. S. Piver, Radioactive colloids in the treatment of stage I-A ovarian cancer, Obstet. Gynecol. 40:42 (1972).PubMedGoogle Scholar
  17. 17.
    A. A. Epenetos, K. E. Hainan, G. Hooker, et al., Antibodyguided irradiation of malignant lesions, Lancet ii:1441 (1984).Google Scholar
  18. 18.
    A. P. Casarett, Modification of radiation injury, in: “Radiation Biology,” A. P. Casarett, ed, Prentice Hall Inc., New Jersey (1968).Google Scholar
  19. 19.
    R. A. Fawwaz, Personal Observation.Google Scholar
  20. 20.
    L. M. Smith, M. Unger, and R. Bartholomew, Anti-mouse responses to monoclonal antibody (MAb) therapy in human patients, J.Nucl. Med. 27:942 (1986).Google Scholar
  21. 21.
    S. M. Larson, J. P. Brown, P. W. Wright, et al., Imaging of melanoma with I-131 labeled monoclonal antibodies, J. Nucl. Med. 24:123 (1983).PubMedGoogle Scholar
  22. 22.
    P. Lo Gerfo, Ting W. Weber C., et al., Immunotherapy of thyroid cancer by induction of thyroiditis, Surgery 94:959 (1983).PubMedGoogle Scholar
  23. 23.
    C. A. Dinarello, R. A. Dempsey, J. W. Mier, et al., Fever, Interleukin-I, and host defense against malignancy, Lymphokine Res. 1:59 (1982).PubMedGoogle Scholar
  24. 24.
    R. A. Fawwaz, F. Frye, and W. Loughman, Survival of skinhomografts in dogs injected with Pd-109-protoporphyrin, J. Nucl. Med. 15:997 (1974).PubMedGoogle Scholar
  25. 25.
    H. Sands, P. L. Jones, S. A. Shah, et al., Factors affecting the uptake of monoclonal “tumor associated” antibodies by human xenografts grown in athymic mice, J. Nucl. Med. 27:922 (1986).Google Scholar
  26. 26.
    G. L. DeNardo, A. Raventos, H. H. Hines, et al., Requirements for a treatment planning system for radioimmunotherapy, Int. J. Radiat. Oncol. Biol. Phys. 11:335 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Rashid A. Fawwaz
    • 1
    • 2
  • Theodore S. T. Wang
    • 1
    • 2
  • Suresh C. Srivastava
    • 1
    • 2
    • 3
  • Rodney Bigler
    • 1
    • 2
    • 4
  • Mark Hardy
    • 1
    • 2
  1. 1.Department of Radiology College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  2. 2.Department of Surgery College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  3. 3.Medical DepartmentBrookhaven National LaboratoryUptonUSA
  4. 4.Division of Nuclear MedicineThe New York Hospital — Cornell Medical CenterNew YorkUSA

Personalised recommendations