INVESTIGADORES
LEVY Estrella Mariel
congresos y reuniones científicas
Título:
Melanoma vaccine of dendritic cells loaded w i t h apoptotic/necrotic cells: characterization and a phase I clinical study
Autor/es:
VON EUW EM; BARRIO MM; FURMAN D; BIANCHINI M; LEVY EM; OLIVIER LANTZ; CASSIAN YEE; YONGQING LI; ALEJANDRA VELLICE; ABRAHAM KOHAN; MORDOH J
Lugar:
Rio de Janeiro
Reunión:
Congreso; 13th International Congress of Immunology, Rio de Janeiro, Brazil, Aug 21-25, 2007; 2007
Institución organizadora:
13th International Congress of Immunology, Rio de Janeiro, Brazil, Aug 21-25, 2007
Resumen:
A melanoma vaccine, DC/Apo-Nec, composed of autologous dendritic cells (DCs) loaded with four apoptotic/necrotic allogeneic melanoma cell lines (Apo-Nec), was developed. Apo-Nec cells were efficiently phagocytosed by immature DCs (iDC) (55±10.5%), and DCs maturation was induced, since FITC-Dextran uptake decreased (iDC: 81±5%; DC/Apo-Nec 33±12%); CD80, CD86, CD83, CCR7, CD40, HLA-I and HLA-II were up-regulated, and in vitro migration to MIP-3â increased. DC/Apo-Nec (HLA-A*0201) induced IFN-ã secretion by CTL clones specific for MART-1 and gp100 Ags, demonstrating efficient cross-presentation. DC/Apo-Nec vaccine was assayed in a Phase I clinical trial in 16 melanoma patients (pts) (1 stage IIC, 7 stage III and 8 stage IV). Cohorts of four pts received four vaccines, containing 5, 10, 15, or 20 x106 DC/Apo-Nec per vaccine. The vaccine was well tolerated; the dose-limiting number of DC/Apo-Nec has not been reached. A positive DTH reaction was observed in all pts after vaccination. CD8+T lymphocytes specific to gp100 and MART-1 Ags were detected by tetramers binding in HLAA* 0201 pts (7/15) before and after vaccination, and increased in 2/7 pts after vaccination. By ELISpot analysis, CD8+T cells specific for MART-1 and gp100 increased 3-14 fold after vaccination in 2/5 pts. With a mean follow-up of 38.5 (22-68) months post-surgery, the stage IIC pt and 7/8 stage III pts are NED; instead, 7/7 stage IV pts have progressed. We conclude that DC/Apo-Nec vaccine is safe, can induce specific immunity against melanoma Ags and in stage III pts it could augment the disease-free survival in the adjuvant setting.
