دورية أكاديمية
A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10-1082 promoter genotype as predictor of disease progression
| العنوان: | A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10-1082 promoter genotype as predictor of disease progression |
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| المؤلفون: | von Euw, E.M., Barrio, M.M., Furman, D., Levy, E.M., Bianchini, M., Peguillet, I., Lantz, O., Vellice, A., Kohan, A., Chacón, M., Yee, C., Wainstok, R., Mordoh, J. |
| المصدر: | J. Transl. Med. 2008;6 |
| سنة النشر: | 2008 |
| المجموعة: | Repositorio Digital Institucional - Universidad de Buenos Aires (RDI UBA) |
| مصطلحات موضوعية: | alpha interferon, B7 antigen, CD8 antigen, CD83 antigen, CD86 antigen, chemokine receptor CCR7, dendritic cell vaccine, dextran, fluorescein isothiocyanate, glycoprotein gp 100, granulocyte macrophage colony stimulating factor, HLA A antigen, HLA antigen class 1, HLA antigen class 2, interleukin 10, interleukin 4, macrophage inflammatory protein 3beta, melan A, melanoma antigen, tetramer, cancer vaccine, abdominal cramp, abdominal pain, adolescent, adult, anorexia, antigen expression, apoptosis, article, asthenia |
| الوصف: | Background: Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic allogeneic melanoma cell lines (Apo-Nec), to evaluate toxicity and immune responses. Also, IL-10 1082 genotype was analyzed in an effort to predict disease progression. Methods: PBMC were obtained after leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines each with 5, 10, 15, or 20 × 106 DC/Apo-Nec cell per vaccine, two weeks apart. Immune responses were measured by ELISpot and tetramer analysis. Il-10 genotype was measured by PCR and corroborated by IL-10 production by stimulated PBMC. Results: Immature DCs efficiently phagocytosed melanoma Apo-Nec cells and matured after phagocytosis as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II, and 75.2 ± 16% reduction in Dextran-FITC endocytosis. CCR7 was also up-regulated upon Apo-Nec uptake in DCs from all patients, and accordingly DC/Apo-Nec cells were able to migrate in vitro toward MIP-3 beta. The vaccine was well tolerated in all patients. The DTH score increased significantly in all patients after the first vaccination (Mann-Whitney Test, p < 0.05). The presence of CD8+T lymphocytes specific to gp100 and Melan A/ MART-1 Ags was determined by ELISpot and tetramer analysis in five HLA-A*0201 patients before and after vaccination; one patient had stable elevated levels before and after vaccination; two increased their CD8 + levels, one had stable moderate and one had negligible levels. The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lower in vitro IL-10 production by stimulated PBMC, and faster melanoma progression ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/20.500.12110/paper_14795876_v6_n_p_vonEuwTest; http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_14795876_v6_n_p_vonEuw_oaiTest |
| الإتاحة: | https://doi.org/20.500.12110/paper_14795876_v6_n_p_vonEuwTest https://hdl.handle.net/20.500.12110/paper_14795876_v6_n_p_vonEuwTest http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_14795876_v6_n_p_vonEuw_oaiTest |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/2.5/arTest |
| رقم الانضمام: | edsbas.2AEE2A0E |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |