Immunogenicity of the Hu14.18-IL2 immunocytokine molecule in adults with melanoma and children with neuroblastoma

Jacquelyn A. Hank, Jacek Gan, Hyunji Ryu, Amy Ostendorf, Michael C. Stauder, Adam Sternberg, Mark Albertini, Kin Ming Lo, Stephen D. Gillies, Jens Eickhoff, Paul M. Sondel

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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/Ib 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.

Original languageEnglish (US)
Pages (from-to)5923-5930
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number18
DOIs
StatePublished - Sep 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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