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Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma
Autor(es) : Bendandi, M. (Maurizio)
Marillonnet, S. (S.)
Kandzia, R. (R.)
Thieme, F. (F.)
Nickstadt, A. (A.)
Herz, S. (S.)
Fröde, R. (R.)
Inoges, S. (Susana)
Lopez-Diaz-de-Cerio, A. (Ascensión)
Soria, E. (Elena)
Villanueva, H. (Helena)
Vancanneyt, G. (G.)
McCormick, A. (A.)
Tuse, D. (D.)
Lenz, J. (J.)
Butler-Ransohoff, J.E. (J.E.)
Klimyuk, V. (V.)
Gleba, Y. (Y.)
Palabras clave : Lymphoma, Non-Hodgkin/immunology
Lymphoma, Non-Hodgkin/therapy
Cancer Vaccines/immunology
Fecha incorporación: 2010
Editorial : Oxford University Press
Versión del editor: http://annonc.oxfordjournals.org/content/21/12/2420
ISSN: 1569-8041
Cita: Bendandi M, Marillonnet S, Kandzia R, Thieme F, Nickstadt A, Herz S, et al. Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma. Ann Oncol 2010 Dec;21(12):2420-2427.
BACKGROUND: Animal and clinical studies with plant-produced single-chain variable fragment lymphoma vaccines have demonstrated specific immunogenicity and safety. However, the expression levels of such fragments were highly variable and required complex engineering of the linkers. Moreover, the downstream processing could not be built around standard methods like protein A affinity capture. DESIGN: We report a novel vaccine manufacturing process, magnifection, devoid of the above-mentioned shortcomings and allowing consistent and efficient expression in plants of whole immunoglobulins (Igs). RESULTS: Full idiotype (Id)-containing IgG molecules of 20 lymphoma patients and 2 mouse lymphoma models were expressed at levels between 0.5 and 4.8 g/kg of leaf biomass. Protein A affinity capture purification yielded antigens of pharmaceutical purity. Several patient Igs produced in plants showed specific cross-reactivity with sera derived from the same patients immunized with hybridoma-produced Id vaccine. Mice vaccinated with plant- or hybridoma-produced Igs showed comparable protection levels in tumor challenge studies. CONCLUSIONS: This manufacturing process is reliable and robust, the manufacturing time from biopsy to vaccine is <12 weeks and the expression and purification of antigens require only 2 weeks. The process is also broadly applicable for manufacturing monoclonal antibodies in plants, providing 50- to 1000-fold higher yields than alternative plant expression methods.
Enlace permanente: http://hdl.handle.net/10171/18677
Aparece en las colecciones: DA - CIMA - Oncología - Inmunoterapia - Artículos de Revista
DA - CUN - Hematología y Hemoterapia - Artículos de revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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