title: Interleukin-2 binds to ganglioside GD(1b).
abstract: We have developed a solid matrix immunoassay to determine the binding of interleukin-2 (IL-2) to specific gangliosides. The assay establishes that recombinant human IL-2 binds to ganglioside GD(1b) but not to any other gangliosides (GM(1), GM(2), GM(3), GD(1a), GD(2), GD(3), and GT(1b)). The binding varies with the ratio of GD1b and IL-2. This assay enables distinguishing the nature of the sugar moiety of the ganglioside recognized by IL-2 and establishes the dosimetry of the ganglioside-IL-2 interaction. Since rIL-2 is administered systematically into stage IV melanoma patients, we have examined 45 tumor biopsies for GD(1b) content. The incidence of GD(1b) in tumor biopsies is 51%. We postulate that GD(1b) associated on the tumor or in the circulation of cancer patients may bind to rIL-2 and prevent the availability of rIL-2 to augment antitumor-immune response.
authors.affiliation: Laboratory of GlycoImmunotherapy, John Wayne Cancer Institute, Santa Monica, California 90404-2302, USA. ravi@jwci.org
authors.forename: M H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: A
authors.initials: A
authors.lastname: Gonzales
authors.forename: D
authors.initials: D
authors.lastname: Soh
authors.forename: K
authors.initials: K
authors.lastname: Nishimoto
authors.forename: W Y
authors.initials: WY
authors.lastname: Tam
authors.forename: A
authors.initials: A
authors.lastname: Bilchik
authors.forename: D L
authors.initials: DL
authors.lastname: Morton
authors.forename: S
authors.initials: S
authors.lastname: O'Day
mesh_terms: D001665:Binding Sites; D005732:Gangliosides / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007118:Immunoassay / Q000379:methods; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D007700:Kinetics; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D005732:Gangliosides; D007376:Interleukin-2; D011994:Recombinant Proteins; C033851:ganglioside, GD1b