Granulocyte-macrophage-colony-stimulating factor added to a multipeptide vaccine for resected Stage II melanoma.
Cancer
; 97(1): 186-200, 2003 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-12491520
ABSTRACT
BACKGROUND:
Forty-eight patients with resected Stages IIA and IIB melanoma were immunized with two tumor antigen epitope peptides derived from gp100(209-217) (210M) (IMDQVPSFV) and tyrosinase(368-376) (370D) (YMDGTMSQV) emulsified with incomplete Freund's adjuvant (IFA). Patients were assigned randomly to receive either peptides/IFA alone or with 250 microm of granulocyte-macrophage-colony-stimulating factor (GM-CSF) subcutaneously daily for 5 days to evaluate the toxicities and immune responses in either arm. Time to recurrence and survival were secondary end points.METHODS:
Immunizations were administered every 2 weeks x 4, then every 4 weeks x 3, and once 8 weeks later. A leukapheresis to obtain peripheral blood mononuclear cells for immune analyses and skin testing with peptides and recall reagents was performed before and after eight vaccinations.RESULTS:
Local pain and granuloma formation, fever, and lethargy of Grade 1 or 2 were observed. Transient vaccine-related Grade III and no Grade IV toxicity was observed. Seventeen of the 40 patients for whom posttreatment skin tests were performed developed a positive skin test response to the gp100 peptide, but only 1 of the 40 patients developed a positive skin test response to tyrosinase. Immune responses were measured by release of interferon-gamma (IFN-gamma) in an enzyme-linked immunosorbent assay (ELISA) by effector cells in the presence of peptide-pulsed antigen-presenting cells, by cytokine release of IFN-gamma, GM-CSF, and tumor necrosis factor-alpha in a Luminex assay, or by an antigen-specific tetramer flow cytometry assay. Thirty-four of the 39 patients for whom the ELISA data were performed demonstrated an immune response after vaccination, as did 37 of 42 patients by tetramer assay. Enzyme-linked immunosorbent assay, Luminex, and tetramer responses in the GM-CSF/peptide/IFA group were higher than in the peptide/IFA group. Epitope spreading to the MART-1/MelanA 27-35 and 26-35 (27L) epitopes was detected by tetramer assay in 10 patients. Seven of 48 patients experienced disease recurrence with a median of 24 months of follow-up and 2 patients in this intermediate to high risk group have died.CONCLUSION:
These data suggest a significant number of patients with resected melanoma mount an antigen-specific immune response against a peptide vaccine. There is a trend for GM-CSF to modestly increase the immune response and support further development of GM-CSF as a vaccine adjuvant.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
/
2_muertes_prematuras_enfermedades_notrasmisibles
Asunto principal:
Neoplasias Cutáneas
/
Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Vacunas contra el Cáncer
/
Melanoma
Tipo de estudio:
Clinical_trials
Límite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cancer
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos