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

J Immunother Emphasis Tumor Immunol. 1996 Jul;19(4):278-95. doi: 10.1097/00002371-199607000-00004.


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 10(6) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Antibodies, Anti-Idiotypic / biosynthesis*
  • Antibodies, Anti-Idiotypic / drug effects
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity
  • Drug Synergism
  • Gangliosides / immunology*
  • Humans
  • Immunoglobulin Idiotypes / immunology*
  • Infusions, Intravenous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacology*
  • Interleukin-2 / therapeutic use
  • Melanoma / immunology*
  • Melanoma / therapy
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy


  • Adjuvants, Immunologic
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Gangliosides
  • Immunoglobulin Idiotypes
  • Interleukin-2
  • Recombinant Proteins
  • ganglioside, GD2