Toward a Better Understanding of Bioassays for the Development of Biopharmaceuticals by Exploring the Structure-Antibody-Dependent Cellular Cytotoxicity Relationship in Human Primary Cells.

Frontiers in Immunology
Sébastien WieckowskiFlorian Cymer

Abstract

Pharmaceutical manufacturing relies on rigorous methods of quality control of drugs and in particular of the physico-chemical and functional characterizations of monoclonal antibodies. To that end, robust bioassays are very often limited to reporter gene assays and the use of immortalized cell lines that are supposed to mimic immune cells such as natural killer (NK) cells to the detriment of primary materials, which are appreciated for their biological validity but are also difficult to exploit due to the great diversity between individuals. Here, we characterized the phenotype of the peripheral blood circulating cytotoxic cells of 30 healthy donors, in particular the repertoire of cytotoxic markers, using flow cytometry. In parallel, we characterized the antibody-dependent cellular cytotoxicity (ADCC) effector functions of these primary cells by measuring their cytolytic activity against a cancer cell-line expressing HER2 in the presence of trastuzumab and with regards to FCGR3A genotype. We could not establish a correlation or grouping of individuals using the data generated from whole peripheral blood mononuclear cells, however the isolation of the CD56-positive population, which is composed not only of NK cells but also of ...Continue Reading

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Methods Mentioned

BETA
glycosylation
flow cytometry
genotyping
PCR
PCA
Assay
FACS
Fluorescence

Software Mentioned

SciPy
Pandas
seaborn
LMFIT
FlowJo
[UNK]
ArcSinh
matplotlib
SoftMax Pro
BD FACSDiva

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