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Production of secretory IgA antibodies in plants

机译：在植物中产生分泌型IgA抗体

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Functional antibodies produced in tobacco plants were first reported over a decade ago (1989). The basic protocol used to generate these 'plantibodies' involved the independent cloning of H and L chain antibody genes in Agrobacterium tumefaciens vectors, the transformation of plant tissue in vitro with the recombinant bacterium, the reconstitution of whole plants expressing individual chains, and their sexual cross. In a 'Mendelian' fashion, a fully assembled and functional antibody was recovered from plant tissue in some double-transgenic plants. In mammalian cells, the antibody H and L chains are produced as precursor proteins that are translocated into the endoplasmic reticulum (ER), under the guidance of signal sequences. Within the ER, the signal peptides are proteolytically cleaved, and several stress proteins act as chaperonins to bind the unassembled antibody chains, and direct subsequent folding and tetramer formation. A similar process occurs in plant cells, and expression can be directed via signal sequences (even of foreign origin) into the aqueous environment of the apoplasm, or to be accumulated in other specific plant tissues, including tubers, fruit, or seed. Plants can facilely assemble secretory IgA, which is comprised of four chains, H and L chains, J chain and secretory component. Plant 'bioreactors' are expected to yield over 10 kg of therapeutic antibody/acre in tobacco, maize, soybean, and alfalfa [(Ann. NY Acad. Sci.) 721(1994)235; (Biotechnol. Bioeng.) 20 (1999) 135]. Compared with conventional steel tank bioreactors using mammalian cells, or microorganisms, the costs of GMP plantibodies are expected to perhaps one tenth. The differences in glycosylation patterns of plant and mammalian cell produced antibodies apparently have no effect on antigen-binding or specificity, but there is some concern about potential immunogenicity in humans. N-linked glycans of plants differ from human by having fucose-linked alpha 1,3 and the sugar xylose. No adverse effects or human anti-mouse antibodies (HAMA) have been observed in ＞40 patients receiving topical oral application of a plant produced secretory IgA specific to Streptococcus mutans, for the control of caries [(Nat. Med.)4(1998)601]. The progressive improvement of expression vectors for plantibodies, and purification strategies, as well as the increase in transformable crop species, is expected to lead to almost limitless availability of inexpensive (even edible forms of) recombinant immunoglobulins free of human pathogens for human and animal therapy, and for novel industrial applications (e.g. catalytic antibodies).
机译：烟草植物中产生的功能性抗体是十多年前（1989年）首次报道的。用于产生这些“植物体”的基本方案包括根癌农杆菌载体中H和L链抗体基因的独立克隆，重组细菌在体外对植物组织的转化，表达单个链的整株植物的重组以及它们的有性繁殖。交叉。以“孟德尔式”的方式，在一些双转基因植物中从植物组织中回收了完全组装且具有功能的抗体。在哺乳动物细胞中，抗​​体H和L链是作为前体蛋白产生的，它们在信号序列的引导下易位到内质网（ER）中。在内质网中，信号肽被蛋白水解切割，并且几种应激蛋白充当伴侣蛋白以结合未组装的抗体链，并指导随后的折叠和四聚体形成。类似的过程发生在植物细胞中，表达可以通过信号序列（甚至是外来的）定向到无浆质的水环境中，或者在其他特定的植物组织中积累，包括块茎，果实或种子。植物可以很容易地组装分泌型IgA，它由4条链，H和L链，J链和分泌成分组成。预计植物“生物反应器”在烟草，玉米，大豆和苜蓿中将产生超过10 kg的治疗性抗体/英亩[（Ann。NY Acad。Sci。）721（1994）235; （Biotechnol.Bioeng。）20（1999）135]。与使用哺乳动物细胞或微生物的常规钢制罐生物反应器相比，GMP植物体的成本预计约为十分之一。植物和哺乳动物细胞产生的抗体糖基化方式的差异显然对抗原结合或特异性没有影响，但是人们对潜在的免疫原性存在一些担忧。植物的N-连接聚糖与人的不同之处在于具有岩藻糖连接的α1,3和糖木糖。在＞ 40名接受局部口服植物产生的变形链球菌特异性分泌型IgA以控制龋齿的＞ 40名患者中，未观察到不良反应或人类抗小鼠抗体（HAMA）[（Nat。Med。）4（1998）。 601]。用于植物体的表达载体的逐步改进和纯化策略，以及可转化农作物种类的增加，有望导致无人病原体的廉价（甚至可食用形式的）重组免疫球蛋白几乎无限地可用于人和动物治疗，以及用于新型工业应用（例如催化抗体）。

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