SYSTEMIC INTERLEUKIN-2 MODULATES THE ANTIIDIOTYPIC RESPONSE TO CHIMERIC ANTI-GD2 ANTIBODY IN PATIENTS WITH MELANOMA

The induction of human antimouse antibodies (HAMA) and human anti-idio typic (anti-Id) responses in cancer patients receiving therapeutic mon oclonal antibody (mAb) may limit the effectiveness of the administered mAb. This report evaluates the influence of systemic interleukin-2 (I L-2) on the anti-Id response to anti-disialoganglioside (anti-GD2) ant ibody given as treatment for patients with melanoma. Twenty-eight pati ents with melanoma received combined immunotherapy with anti-GD2 antib ody and IL-2 at 1.5 x 10(6) U/m(2)/day given 4 days/week, The anti-GD2 antibody [murine 14.G2a mAb; dose levels of 2-5 mg/m(2)/day (4 patien ts); or human-mouse chimeric 14.18 (ch14.18) antibody; dose levels of 2-10 mg/m(2)/day (24 patients)] was scheduled to be given for 5 days e ither before, during, or after initial systemic IL-2 treatment. All fo ur patients who received murine 14.G2a developed HAMA anti-isotype ant ibodies (660-1,000 ng/ml) as well as measurable anti-Id antibodies. Al l three patients who received initial treatment with ch14.18 alone dev eloped a strong anti-Id antibody response after IL-2 was started 1 wee k later. The serum level of anti-Id antibody decreased during subseque nt ch 14.18 infusions, suggesting that the anti-Id antibody may be bin ding the administered ch14.18. In contrast, measurable anti-Id antibod y was detected in only 3 of 14 patients who received IL-2 before, duri ng, and after initial ch14.18 administration. Two of four patients rec eiving 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 tha t 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, durin g, and after the antibody administration.