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A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a

Summary

Nine patients with neuroblastoma stage IV were treated with the murine monoclonal antibody 14.G2a, directed against disialoganglioside GD2. The antibody was injected daily for 5–10 days and the total applied dosage ranged between 100 mg/m2 and 400 mg/m2. The peak serum levels of mAb 14.G2a ranged from 28 µg/ml to 61 µg/ml. Pharmacokinetic data obtained in three patients indicated that the serum elimination of mAb 14.G2a fits a two-compartment model, with an α-half-time (t 1/2α ) between 0.66 h and 1.98 h and a β-half-time (t 1/2β ) between 30.13 h and 53.33 h. All patients presented with a human anti-(mouse IgG) antibody response either during or shortly after therapy. Eight patients showed a continuous decrease in complement component C4 during therapy, as well as an initial decrease in C3c and an initial increase in C3a, all suggesting an activation of the complement cascade. Side-effects consisted of allergic reactions like pruritus, exanthema, urticaria and of severe pain, predominantly located in the abdomen and lower extremities, which required the use of continuous intravenous morphine. Four patients additionally developed a transient hypertension and one patient experienced a transient nephrotic syndrome. Three patients were treated in an adjuvant setting and are not evaluable for tumor response. Of the remaining six patients, two had a complete remission, two showed a partial remission, and two patients did not respond to treatment.

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References

  1. 1.

    Barker E, Mueller BM, Handgretinger R, Herter M, Yu AL, Reisfeld RA (1991) Effect of a chimeric antiganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res 51: 144

  2. 2.

    Cheung NK, Landmeier B, Neely J, Nelson AD, Abramowsky C, Ellery S, Adams RB, Miraldi F (1986) Complete ablation with iodine131-radiolabeled disialoganglioside GD2-specific monoclonal antibody against human neuroblastoma xenografted in nude mice. J Natl Cancer Inst 77: 739

  3. 3.

    Cheung NK, Lazarus H, Miraldi F, Abramowsky C, Kallick S, Saarinen U, Spitzer T, Strandjord S, Coccia P, Berger N (1987) Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol 5: 1430

  4. 4.

    Conrad A, Schürmann J, Kreutz FH, Sieber A (1978) Elaboration of a method for the quantitative determination of proteins by laser nephelometry in the clinical routine laboratory. J Clin Chem Clin Biochem 16: 229

  5. 5.

    Dopfer R, Berthold F, Einsele H, Ehninger G, Klingebiel T, Handgretinger R, Bruchelt G, Niethammer D, Stollmann B, Rister M, Bender-Götze C (1989) Bone marrow transplantation in children with neuroblastoma. Folia Haematol 116: 427

  6. 6.

    Evans AE, D'Angio GJ, Randolph J (1971) A proposed staging with neuroblastoma. Cancer 27: 374

  7. 7.

    Mujoo K, Cheresh DA, Yang HM, Reisfeld RA (1987) Disialoganglioside GD2 on human neuroblastoma cells: target antigen for monoclonal antibody-mediated cytolysis and suppression of tumor growth. Cancer Res 47: 1098

  8. 8.

    Mujoo K, Kipps TJ, Yang HM, Cheresh DA, Wargalla W, Sander D, Reisfeld RA (1989) Functional properties and effect on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal anti-ganglioside GD2 antibody 14.18. Cancer Res 49: 2857

  9. 9.

    Müller-Eberhard HJ (1983) Complement abnormalities in human disease. In: The biology of immunologic disease. Sinauer Associates, Sunderland, Mass., p 167

  10. 10.

    Saarinen UM, Coccia PF, Gerson SL, Pelley R, Cheung NKV (1985) Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: method for purging autologous bone marrow. Cancer Res 45: 5969

  11. 11.

    Schulz G, Cheresh DA, Varki NM, Yu A, Staffileno LK, Reisfeld RA (1984) Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Res 44: 5914

  12. 12.

    Treuner J, Gerein V, Klingebiel T, Schwabe D, Feine U, Happ J, Niethammer D, Maul F, Dopfer R, Kornhuber B, Berthold F, Jürgens H, Hör G (1988) MIBG-treatment in neuroblastoma: experiences of the Tübingen/Frankfurt group. In: Evans/D'Angio/Seeger: Advances in neuroblastoma research. Liss, New York, p 669

  13. 13.

    Wagner JG (1975) Mathematical model for serum elimination of antibodies: In: Fundamentals of pharmacokinetics. Druf Intelligence, Hamilton, Ill., p 80

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Correspondence to Rupert Handgretinger.

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Supported by the Deutsche Krebshilfe

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Handgretinger, R., Baader, P., Dopfer, R. et al. A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a. Cancer Immunol Immunother 35, 199–204 (1992). https://doi.org/10.1007/BF01756188

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Key words

  • Immunotherapy
  • Anti-GD2 antibody
  • Neuroblastoma