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Systemic interleukin-2 modulates the anti-idiotypic response to chimeric anti-GD2 antibody in patients with melanoma.
- Source :
-
Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy [J Immunother Emphasis Tumor Immunol] 1996 Jul; Vol. 19 (4), pp. 278-95. - Publication Year :
- 1996
-
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 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.
- Subjects :
- Antibodies, Anti-Idiotypic drug effects
Antibodies, Monoclonal immunology
Antibody-Dependent Cell Cytotoxicity
Drug Synergism
Humans
Infusions, Intravenous
Interleukin-2 administration & dosage
Interleukin-2 therapeutic use
Melanoma therapy
Recombinant Proteins administration & dosage
Recombinant Proteins immunology
Recombinant Proteins therapeutic use
Skin Neoplasms immunology
Skin Neoplasms therapy
Adjuvants, Immunologic pharmacology
Antibodies, Anti-Idiotypic biosynthesis
Antibodies, Monoclonal therapeutic use
Gangliosides immunology
Immunoglobulin Idiotypes immunology
Interleukin-2 pharmacology
Melanoma immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1067-5582
- Volume :
- 19
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 8877722
- Full Text :
- https://doi.org/10.1097/00002371-199607000-00004