title: Biological Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated With GM-CSF (Sargramostim) as Adjuvant Therapy of Melanoma.
abstract: OBJECTIVE
  We investigated the development of binding and neutralizing antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients receiving prolonged therapy with GM-CSF as adjuvant therapy of melanoma and the impact of these antibodies on biological effects.
  
  
  METHODS
  Fifty-three patients with high-risk melanoma that had been surgically excised were treated with GM-CSF, 125 μg/m daily for 14 days every 28 days for 1 year after surgical resection of disease. Serum samples for antibodies to GM-CSF were measured before treatment and on study days 155 and 351. Blood draws for testing biological effects were keyed to GM-CSF administration: days 0 (before), 15 (after 14 d on GM-CSF), 29 (after 14 d off GM-CSF), 155, and 351 (after 14 d on GM-CSF in the sixth and 13th cycle of treatment).
  
  
  RESULTS
  Of 53 patients enrolled, 43 were evaluable for the development of anti-GM-CSF antibodies. Of these, 93% developed binding antibodies and 42% developed both binding and neutralizing antibodies. The increase in the white blood cell count, percent eosinophils, or neopterin levels engendered by GM-CSF administration was abrogated or markedly decreased in patients with neutralizing antibodies but not in patients who developed only binding antibodies.
  
  
  CONCLUSIONS
  Ninety-three percent of patients with melanoma treated with GM-CSF as adjuvant therapy develop antibodies to GM-CSF. In those with neutralizing antibodies, a diminution of the biological effects of GM-CSF was observed. The development of neutralizing antibodies might also abrogate the potential clinical benefit of this treatment and should be considered in the design of future clinical trials.
authors.affiliation: *Northern California Melanoma Center, St. Mary's Medical Center, San Francisco §Scott Cruickshank & Associates, Santa Barbara, CA ‡Hillman Cancer Center, The University of Pittsburgh, Pittsburgh, PA †Syrinx Bioanalytics Oy, Turku, Finland.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Spitler
authors.forename: Huynh
authors.initials: H
authors.lastname: Cao
authors.forename: Timo
authors.initials: T
authors.lastname: Piironen
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: Robert W
authors.initials: RW
authors.lastname: Weber
authors.forename: Scott
authors.initials: S
authors.lastname: Cruickshank
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000276:immunology*; D001686:Biological Phenomena; D017024:Chemotherapy, Adjuvant; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D007155:Immunologic Factors; D011994:Recombinant Proteins; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor