Immunogenicity of the Hu14.18-IL2 Immunocytokine Molecule in Adults With Melanoma and Children With Neuroblastoma

Purpose: Immunocytokine (IC) hu14.18-IL2 is a fusion protein of humanized antidisialoganglioside (GD2) antibody (hu14.18) and interleukin (IL)-2. Sixty-one melanoma and neuroblastoma patients received IC in phase I/lb studies. Patient sera were examined in ELISA to determine if an anti-IC antibody response occurred during treatment. Experimental Design: Serum was assayed for anti-idiotypic antibody (anti-id Ab) based on ability to bridge biotinylated hu14.18 to plate-bound hu14.18 and ability to inhibit binding of hu14.18 to GD2 antigen and/or murine anti-idiotypic antibody. ELISA was also used to detect antibodies to the Fc-IL2 end of hu14.18-IL2. Results: Thirty-two patients (52%) developed an anti-idiotypic antibody response (absorbance, > 0.7) in the bridge ELISA. Twelve patients (20%) had an intermediate response, whereas 17 patients (28%) were negative (adsorbance, < 0.3). The development of antibody to hu14.18-IL2 detected in the bridge ELISA was not related to the dose of hu14.18-IL2. Twenty of 33 adult patients (61%) demonstrated an anti-idiotypic antibody response based on binding inhibition ELISA. The anti-idiotypic response was inversely correlated (P < 0.002) with IC measured during the second course of treatment, indicating that development of anti-idiotypic antibodies interfered with detection of circulating hu14.18-IL2. All patients developed some inhibitory activity in the binding inhibition assay designed to detect antibodies to the Fc-IL2 region of the IC. There was a positive correlation between the peak serum level of IC in course 1 and the anti-Fc-IL2 response. Conclusions: Patients treated with hu14.18-IL2 developed anti-idiotypic antibodies and anti Fc-IL2 antibodies. No association was seen between development of anti-IC antibodies and clinical toxicity. (Clin Cancer Res 2009;15(18):5923-30)