title: The development of anti-interleukin-2 (IL-2) antibodies in cancer patients treated with recombinant IL-2.
abstract: Serum samples from 217 cancer patients participating in phase I/II clinical trials were analysed for the development of anti-interleukin-2 (IL-2) antibodies. Patients received recombinant human IL-2 (rIL-2) by continuous intravenous infusion (c.i.v.; n = 86) or by subcutaneous (s.c.) injections (n = 131). Both patient groups developed anti-rIL-2 antibodies as detected by ELISA with similar frequencies and titres: 52% (median titre, 23) and 47% (median titre, 24), respectively. Using an IL-2-dependent T-cell proliferation assay, sera from 5 c.i.v.-treated patients (6%) and 13 s.c.-treated patients (10%) exhibited neutralising activity. Immunoabsorption studies with rIL-2-coated beads, demonstrated that in 8 of 15 patients with neutralising sera, the neutralising activity was correlated with specific anti-rIL-2 immunoglobulin. All 8 patients had received at least two cycles of rIL-2 by s.c. injections. Specific IL-2 neutralising activity affected both recombinant and natural IL-2 in all 8 patients. Development of anti-rIL-2 antibodies, irrespective of whether these exhibited neutralising activity or not, did not affect the frequency or duration of clinical responses.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Scharenberg
authors.forename: A G
authors.initials: AG
authors.lastname: Stam
authors.forename: B M
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: G J
authors.initials: GJ
authors.lastname: Roest
authors.forename: P A
authors.initials: PA
authors.lastname: Palmer
authors.forename: C R
authors.initials: CR
authors.lastname: Franks
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D000912:Antibodies, Neoplasm / Q000097:blood*; D000917:Antibody Formation; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000276:immunology* / Q000627:therapeutic use; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D011994:Recombinant Proteins