In vitro models for immunogenicity prediction of therapeutic proteins.

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.

Hydrogels in three-dimensional dendritic cell (MUTZ-3) culture as a scaffold to mimic human immuno competent subcutaneous tissue.

The objective of this study was to develop a 3D cell culture model of the human subcutaneous tissue, allowing the prediction of the immunogenicity of subcutaneously injected therapeutic proteins. Several hydrogels were evaluated as scaffolds to mimic the human subcutaneous tissue in vitro. Cytocompatibility of the hydrogels with the human myelomonocytic cell line (MUTZ-3) was investigated, as well as their influence on cellular phenotype changes.