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


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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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