Systemic interleukin-2 modulates the anti-idiotypic response to chimeric anti-GD2 antibody in patients with melanoma

Mark R. Albertini, Jacek Gan, Peter Jaeger, Jacquelyn A. Hank, Barry Storer, Kathy Schell, Tammy Rivest, Jean Surfus, Ralph A. Reisfeld, Joan H. Schiller, Paul M. Sondel

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22 Scopus citations

Abstract

The induction of human antimouse antibodies (HAMA) and human anti- idiotypic (anti-Id) responses in cancer patients receiving therapeutic monoclonal antibody (mAb) may limit the effectiveness of the administered mAb. This report evaluates the influence of systemic interleukin-2 (IL-2) on the anti-Id response to anti-disialoganglioside (anti-GD2) antibody given as treatment for patients with melanoma. Twenty-eight patients with melanoma received combined immunotherapy with anti-GD2 antibody and IL-2 at 1.5 x 106 U/m2/day given 4 days/week. The anti-GD2 antibody [murine 14.G2a mAb; dose levels of 2-5 mg/m2/day (4 patients); or human-mouse chimeric 14.18 (ch14.18) antibody; dose levels of 2-10 mg/m2/day (24 patients)] was scheduled to be given for 5 days either before, during, or after initial systemic IL-2 treatment. All four patients who received murine 14.G2a developed HAMA anti-isotype antibodies (660-1,000 ng/ml) as well as measurable anti-Id antibodies. All three patients who received initial treatment with ch14.18 alone developed a strong anti-Id antibody response after IL-2 was started 1 week later. The serum level of anti-Id antibody decreased during subsequent ch14.18 infusions, suggesting that the anti-Id antibody may be binding the administered ch14.18. In contrast, measurable anti-Id antibody was detected in only 3 of 14 patients who received IL-2 before, during, and after initial ch14.18 administration. Two of four patients receiving systemic IL-2 before and during initial ch14.18 infusions, and two of three patients receiving systemic IL-2 concurrent with initial ch14.18 infusions developed anti-Id antibodies. These data suggest that the anti-Id response to chimeric anti-GD2 antibody is influenced by the timing of systemic IL-2 in relation to antibody administration and can be suppressed by systemic treatment with IL-2 given before, during, and after the antibody administration.

Original languageEnglish (US)
Pages (from-to)278-295
Number of pages18
JournalJournal of Immunotherapy
Volume19
Issue number4
Publication statusPublished - 1996

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Keywords

  • Anti-idiotypic antibodies
  • Antibody-dependent cellular cytotoxicity
  • Human antimouse antibodies
  • Interleukin-2

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Albertini, M. R., Gan, J., Jaeger, P., Hank, J. A., Storer, B., Schell, K., ... Sondel, P. M. (1996). Systemic interleukin-2 modulates the anti-idiotypic response to chimeric anti-GD2 antibody in patients with melanoma. Journal of Immunotherapy, 19(4), 278-295.