title: Immunogenicity of the hu14.18-IL2 immunocytokine molecule in adults with melanoma and children with neuroblastoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: The University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin 53792, USA. hank@humonc.wisc.edu
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Hank
authors.forename: Jacek
authors.initials: J
authors.lastname: Gan
authors.forename: Hyunji
authors.initials: H
authors.lastname: Ryu
authors.forename: Amy
authors.initials: A
authors.lastname: Ostendorf
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stauder
authors.forename: Adam
authors.initials: A
authors.lastname: Sternberg
authors.forename: Mark
authors.initials: M
authors.lastname: Albertini
authors.forename: Kin-Ming
authors.initials: KM
authors.lastname: Lo
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gillies
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sondel
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D045744:Cell Line, Tumor; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; C493743:lorukafusp alfa