Immunogenicity of glycans on biotherapeutic drugs produced in plant expression systems - the taliglucerase alfa story

Plants are a promising alternative for the production of biotherapeutics. Manufacturing in-planta adds plant specific glycans. To understand immunogenic potential of these glycans, we developed a validated method to detect plant specific glycan antibodies in human serum. Using this assay, low prevalence of pre-existing anti-plant glycan antibodies was found in healthy humans (13.5%) and in glucocerebrosidase-deficient Gaucher disease (GD) patients (5%). A low incidence (9% in naïve patient and none in treatment experienced patients) of induced anti-plant glycan antibodies was observed in GD patients after up to 30 months replacement therapy treatment with taliglucerase alfa, a version of human glucocerebrosidase produced in plant cells. Detailed evaluation of clinical safety and efficacy endpoints indicated that anti-plant glycan antibodies did not affect the safety or efficacy of taliglucerase alfa in patients. This study shows the benefit of using large scale human trials to evaluate ...植物是生产生物治疗药物的极具前景的替代方案。在植物体内进行生产会引入植物特异性聚糖（plant specific glycans）。为阐明此类聚糖的免疫原性潜力，我们开发了一种经过验证的方法，可在人类血清中检测植物特异性聚糖抗体。利用该检测方法，我们发现健康人群（13.5%）与葡糖脑苷脂酶（glucocerebrosidase）缺乏型戈谢病（Gaucher disease, GD）患者（5%）体内预先存在的抗植物聚糖抗体患病率较低。在接受长达30个月的阿糖苷酶α（taliglucerase alfa，一种在植物细胞中生产的人葡糖脑苷脂酶制剂）替代治疗的GD患者中，观察到诱导型抗植物聚糖抗体的发生率较低：初治患者为9%，经治患者则未检测到该抗体。对临床安全性与有效性终点的详细评估显示，抗植物聚糖抗体不会影响阿糖苷酶α在患者体内的安全性与有效性。本研究证实了开展大规模人体试验以评估[...]的价值。