Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma
Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma
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DOI：
10.1093/annonc/mdq256
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发表时间：
2010-12-01
影响因子：
50.5
通讯作者：
Gleba, Y.
中科院分区：
文献类型：
--
作者：
Bendandi, M.;Marillonnet, S.;Gleba, Y.
设计图：我们报告了一种新的疫苗生产工艺，magnifection，没有上述缺点，并允许一致和有效的表达在植物中的全免疫球蛋白（Igs）。结果：完整的独特型（Id）的20例淋巴瘤患者和2个小鼠淋巴瘤模型的IgG分子表达在0.5和4.8 g/kg的叶生物量之间的水平。蛋白A亲和捕获纯化产生药物纯度的抗原。在植物中产生的几个病人的免疫球蛋白表现出特异性的交叉反应性与血清来自同一患者用杂交瘤生产的Id疫苗免疫。用植物或杂交瘤产生的免疫球蛋白接种的小鼠在肿瘤攻击study.Conclusions中显示出相当的保护水平：这种制造过程是可靠和稳健的，从活检到疫苗的制造时间< 12周，抗原的表达和纯化仅需2周。该方法也广泛适用于在植物中生产单克隆抗体，提供比替代植物表达方法高50至1000倍的产量。
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.