Immunotoxins pp 475-480 | Cite as

Human immune response to immunotoxins

  • Andrew A. Hertler
Part of the Cancer Treatment and Research book series (CTAR, volume 37)


The potential value of immunotoxins (ITs) in the treatment of human cancer may eventually prove to be limited by the development of host antibodies against the conjugate. The development of antimurine antibodies after administration of unconjugated monoclonal antibodies is well documented and has been associated with more rapid murine antibody clearance and decreased clinical effect [1, 2]. Similarly, antitoxin antibodies have been detected in both animals and humans treated with ricin and abrin [3, 4]. When given lethal doses of ricin, survival was prolonged in mice which had developed antiricin antibody levels in excess of 10–20 ng/ml [3].


Chronic Lymphocytic Leukemia Human Immune Response Polyethylene Glycol Adenosine Deaminase Serum Sickness 
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  1. 1.
    Sawler, D.L., Bartholomew, R.M., Smith, L.M., and Dillman, R.O. (1985) Human immune response to multiple injections of murine monoclonal IgG. J. Immunol., 135, 1530–1535.Google Scholar
  2. 2.
    Schroff, R.W., Foon, K.A., Beatty, S.M., Oldham, R.K., and Morgan, A.C. (1985) Human anti-murine immunoglobulin response in patients receiving monoclonal antibody therapy, Cancer Res., 45, 879–885.PubMedGoogle Scholar
  3. 3.
    Godal, A., Fodstad, O., and Pihl, A. (1983) Antibody formation against the cytotoxic proteins abrin and ricin in humans and mice. Int. J. Cancer, 32, 515–521.PubMedCrossRefGoogle Scholar
  4. 4.
    Fodstad, O., Kvalheim, G., Godai, A., Lotsberg, J., Aadmal, S., Host, H., and Pihl, A. (1984) Phase I study of the plant protein ricin. Cancer Res., 44, 862–865.PubMedGoogle Scholar
  5. 5.
    Harkonen, S., Stoudemire, Jr., Mischak, R., Spitler, L.E., Lopez, H., and Scannon, P. (1987) Toxicity and immunogenicity of monoclonal antimelanoma antibody-ricin A chain immunotoxin in rats. Cancer Res., 47, 1377–1382.PubMedGoogle Scholar
  6. 6.
    Ramakrishnan, S., and Houston, L.L. (1982) Prevention of growth of leukemia cells in mice by monoclonal antibodies directed against Thy 1.1 antigen disulfide linked to two ribosomal inhibiters: Pokeweed antiviral protein or ricin A chain. Cancer Res., 44, 1398–1404.Google Scholar
  7. 7.
    Hertler, A.A., Schlossman, D.M., Lester, C., Balis, F., Thorpe, P., Poplack, D., and Frankel, A. (1987) Intrathecal administration of WT1-ricin A chain immunotoxin. Proc. of ASCO, 5, 989, pg 251.Google Scholar
  8. 8.
    Spitler, L.E., del Rio, M., Khentigan, A., Wedel, N.I., Brophy, N.A., Miller, L.L., Harkonen, W.S., Rosendorf, L.L., Lee, H.M., Mischak, R.P., Kawahata, R.T., Stoudemire, J.B., Fradkin, L.B., Bautista, E.F., and Scannon, P.J. (1987) Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin Cancer Res., 47, 1717–1723.PubMedGoogle Scholar
  9. 9.
    Laurent, G., Pris, J., Farcet, J.P., Carayon, P., Blythman, H., Casellas, P., Poncelet, P., and Jansen, F.K. (1986) Effects of therapy with T101 ricin-A-chain immunotoxin in two leukemia patients. Blood, 67, 1680–1687.PubMedGoogle Scholar
  10. 10.
    Hertler, A.A., Schlossman, D.M., Borowitz, M.J., Laurent, G., Jansen, F.K., Schmidt, C., and Frankel, A.E. A phase I study of T101-ricin A-chain immunotoxin in refractory chronic lymphocytic leukemia, submitted for publication.Google Scholar
  11. 11.
    Moolten, F.L., Capparell, N.J., and Zajdel, S.H. (1975) Antitumor effects of antibody-diphtheria toxin conjugates. III. Cyclophosphamide induced immune unresponsiveness to conjugates. J. Natl. Cancer Inst., 55, 709–712.PubMedGoogle Scholar
  12. 12.
    Jaffers, G.J., Colvin, R.B., Cosimi, A.B., Giorgi, J.V., Goldstein, G., Fuller, T.C., Kurnick, J.T., Lillehei, C., and Russell, P.S. (1983) The human immune response to murine OKT3 monoclonal antibody. Transplant Proc., 15, 646–648.Google Scholar
  13. 13.
    Abuchowski, A., van Es, T., Palczuk, N.C., and Davis, F.F. (1977) Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J. Biochem., 252, 3578–3581.Google Scholar
  14. 14.
    Abuchowski, A., van Es, T., Palczuk, N.C., McCoy, J.R., and Davis, F.F. (1979) Treatment of L5178Y tumor-bearing BDF, mice with a nonimmunogenic L-glutaminase-Lasparaginase. Cancer Treat. Rep., 63, 1127–1132.PubMedGoogle Scholar
  15. 15.
    Davis, S., Abuchowski, A., Park, Y.K., and Davis, F.F. (1981) Alteration of the circulating life and antigenic properties of bovine adenosine deaminase in mice by attachment of polyethylene glycol. Clin. Exp. Immunol., 46, 649–652.PubMedGoogle Scholar
  16. 16.
    Hershfield, M.S., Buckley, R.H., Greenberg, M.L., Melton, A.L., Schiff, R., Hatem, C., Kurtzberg, J., Markert, M.L., Kobayashi, R.H., Kobayashi, A.L., and Abuchowski, A. (1987) Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N. Engl. J. Med., 316, 589–596.PubMedCrossRefGoogle Scholar

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© Kluwer Academic Publishers 1988

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  • Andrew A. Hertler

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