In vitro models for immunogenicity prediction of therapeutic proteins

Floriane Groell; Olivier Jordan; Gerrit Borchard

doi:10.1016/j.ejpb.2018.06.008

In vitro models for immunogenicity prediction of therapeutic proteins

Eur J Pharm Biopharm. 2018 Sep:130:128-142. doi: 10.1016/j.ejpb.2018.06.008. Epub 2018 Jun 9.

Authors

Floriane Groell¹, Olivier Jordan¹, Gerrit Borchard²

Affiliations

¹ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Médical Universitaire (CMU), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
² School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Centre Médical Universitaire (CMU), Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: Gerrit.Borchard@unige.ch.

PMID: 29894817
DOI: 10.1016/j.ejpb.2018.06.008

Abstract

Immunogenicity assessment of therapeutic proteins is routinely performed through various techniques during the drug development process: (i) in silico to design the least immunogenic protein possible, (ii) in vitro using mainly classic 2D assays with PBMC-derived cells or immune cell lines to follow protein uptake, immune cell maturation and pro-inflammatory cytokines released, (iii) in vitro using 3D models of the human immune lymphatic system or full-thickness skin, (iv) and finally in vivo with preclinical and clinical studies. This review focuses primarily on the immunogenicity assessment of therapeutic proteins injected subcutaneously and new in vitro models that may be used as specific models of this tissue.

Keywords: Immunogenicity assessment; In vitro model; Injection site reactions; Subcutaneous injection; Therapeutic protein.

Publication types

Review

MeSH terms

Animals
Computer Simulation
Cytokines / immunology
Drug Design*
Drug Evaluation, Preclinical / methods
Humans
Leukocytes, Mononuclear / immunology
Models, Biological*
Proteins / immunology*

Substances

Cytokines
Proteins