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

• Published in: PloS one Vol. 12; no. 10; p. e0186211
• Main Authors: Rup, Bonita, Alon, Sari, Amit-Cohen, Bat-Chen, Brill Almon, Einat, Chertkoff, Raul, Tekoah, Yoram, Rudd, Pauline M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2017; Public Library of Science (PLoS)
• Subjects: Analysis; Antibodies; Biological Products; Biology and Life Sciences; Blood & organ donations; Carbohydrates; Clinical trials; Disease; Dosage and administration; Double-Blind Method; Drugs; Engineering and Technology; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Gaucher Disease - drug therapy; Gaucher's disease; Glucosylceramidase; Glucosylceramidase - biosynthesis; Glucosylceramidase - therapeutic use; Glycan; Glycosylation; Health aspects; Humans; Immune response; Immunoassay; Immunogenicity; Immunoglobulins; Laboratory animals; Male; Mammals; Medicine and Health Sciences; Patients; Pediatrics; Pharmaceuticals; Plant cells; Plants (botany); Plants - genetics; Polysaccharides; Polysaccharides - immunology; Product development; Production capacity; Proteins; R&D; Research & development; Research and Analysis Methods; Safety; Studies; Therapeutics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186211

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 the immunogenicity risk of plant derived glycans, and indicates no apparent risk related to anti-plant glycan antibodies.