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

PLoS One. 2017 Oct 31;12(10):e0186211. doi: 10.1371/journal.pone.0186211. eCollection 2017.

Abstract

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Biological Products*
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gaucher Disease / drug therapy
  • Glucosylceramidase / biosynthesis*
  • Glucosylceramidase / therapeutic use
  • Glycosylation
  • Humans
  • Male
  • Plants / genetics*
  • Polysaccharides / immunology*

Substances

  • Biological Products
  • Polysaccharides
  • Glucosylceramidase
  • taliglucerase alfa

Grant support

SA, BA-C, EBA, RC and YT are current employees of Protalix Ltd.; BR is an employee of Bonnie Rup Consulting, LLC and a previous employee of Pfizer Inc; The Andover/Cambridge PDM Clinical Assay Development group are current or previous employees of Pfizer Inc. and have contributed to the study design; Because of these authors' status as current or past employees of the study sponsors, the sponsors participated in study design, data collection and analysis, decision to publish, and preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.