A versatile cell-based assay to assess therapeutic antigen-specific PD-1-targeted approaches

Katrijn Broos, Maarten Versteven, Jphan MJ Van de Bergh, Quentin Lecocq, Diana Campillo-Davo, Hans De Reu, Fumihiro Fujiki, Soyoko Morimoto, Marleen Keyaerts, Bart Neyns, Haruo Sugiyama, Viggo Fi Van Tendeloo, Karine Breckpot, Eva Lion

Onderzoeksoutput: Unpublished paper

Samenvatting

Blockade of inhibitory programmed death-1 (PD-1) immune checkpoint signaling is a promising cancer treatment.
Successful clinical trials using monoclonal antibodies targeting the PD-1/PD-L1 pathway have boosted preclinical
research in this field and encouraged the development of novel blocking moieties. However, developing a
standardized assay to evaluate the blocking capacity of novel therapeutics remains challenging. Several biotech
companies have brought robust and short-term bio-assays to the market, nevertheless all lacking antigen
specificity.
Here, we developed a multiparametric, uncomplicated and high-throughput T cell assay with antigen-specific
properties. We designed a PD-1 negative and PD-1 positive T-cell receptor (TCR)-deficient 2D3 cell line, which
becomes eGFP positive when activated due to its nuclear factor of activated T-cell (NFAT) eGFP promotor. By
transfection of messenger RNA encoding for any TCR of interest, this assay allows the evaluation of therapeutics
targeting the PD-1/PD-L1 pathway in an
antigen-specific manner. We were able to demonstrate a reduction in antigen-specific T cell activity when the
PD-1/PD-L1 pathway was activated by PD-L1 positive antigen-presenting cells, demonstrated by decreased eGFP
expression. Furthermore, addition of anti-PD-1 or anti-PD-L1 antibodies could restore the eGFP expression. Our
assay encourages studies on antigen-specific immune checkpoint therapy by providing a valuable tool to evaluate
PD-1 or PD-L1-targeted moieties.
Originele taal-2English
StatusPublished - 30 sep 2017
EvenementBIS meeting - Leuven, Belgium
Duur: 23 nov 201723 nov 2017

Conference

ConferenceBIS meeting
LandBelgium
Periode23/11/1723/11/17

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