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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.
Spitler, Lynn E; Cao, Huynh; Piironen, Timo; Whiteside, Theresa L; Weber, Robert W; Cruickshank, Scott.
Afiliação
  • Spitler LE; *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.
Am J Clin Oncol ; 40(2): 207-213, 2017 Apr.
Article em En | MEDLINE | ID: mdl-25286079
OBJECTIVES: 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator Estimulador de Colônias de Granulócitos e Macrófagos / Anticorpos Neutralizantes / Fatores Imunológicos / Melanoma Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Clin Oncol Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Finlândia

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator Estimulador de Colônias de Granulócitos e Macrófagos / Anticorpos Neutralizantes / Fatores Imunológicos / Melanoma Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Clin Oncol Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Finlândia