Annals of oncology, 2010-12, Vol.21 (12), p.2420-2427
2010
Details
- Autor(en) / Beteiligte
- Titel
- Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma
- Ist Teil von
- Annals of oncology, 2010-12, Vol.21 (12), p.2420-2427
- Ort / Verlag
- Oxford: Elsevier Ltd
- Erscheinungsjahr
- 2010
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. 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). 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0923-7534eISSN: 1569-8041DOI: 10.1093/annonc/mdq256Titel-ID: cdi_proquest_miscellaneous_812128216
- Format
- –
- Schlagworte
- Agrobacterium tumefaciens - genetics, Agrobacterium tumefaciens - immunology, Agrobacterium tumefaciens - metabolism, Animals, Antineoplastic agents, Biological and medical sciences, Cancer Vaccines - biosynthesis, Cancer Vaccines - genetics, Cancer Vaccines - immunology, Cancer Vaccines - isolation & purification, Cloning, Molecular, Efficiency, Gene Expression Regulation, Plant, Hematologic and hematopoietic diseases, Humans, idiotype, Immunoglobulin Idiotypes - genetics, Immunoglobulin Idiotypes - immunology, Immunoglobulin Idiotypes - metabolism, Individuality, Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis, lymphoma, Lymphoma, Non-Hodgkin - immunology, Lymphoma, Non-Hodgkin - therapy, magnifection, Medical sciences, Mice, Mice, Inbred C3H, Pharmacology. Drug treatments, plant-produced, Plantibodies - genetics, Plantibodies - isolation & purification, Plantibodies - metabolism, Plants, Genetically Modified - genetics, Plants, Genetically Modified - immunology, Plants, Genetically Modified - metabolism, recombinant, Time Factors, vaccine, Vaccines, Synthetic - biosynthesis, Vaccines, Synthetic - genetics, Vaccines, Synthetic - immunology, Vaccines, Synthetic - isolation & purification