Details

Autor(en) / Beteiligte

• Lee, Ho Young
• Contreras, Edward
• Register, Ames C.
• Wu, Qiang
• Abadie, Kathleen
• Garcia, Khristofer
• Wong, Pin Yee
• Jiang, Guoying

Titel

Development of a bioassay to detect T-cell-activating impurities for T-cell-dependent bispecific antibodies

Ist Teil von

• Scientific reports, 2019-03, Vol.9 (1), p.3900-3900, Article 3900

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• T-cell-dependent bispecific antibodies (TDBs) are promising cancer immunotherapies that recruit a patient’s T cells to kill cancer cells. There are increasing numbers of TBDs in clinical trials, demonstrating their widely recognized therapeutic potential. Due to the fact that TDBs engage and activate T cells via an anti-CD3 (aCD3) arm, aCD3 homodimer (aCD3 HD) and high-molecular-weight species (HMWS) are product-related impurities that pose a potential safety risk by triggering off-target T-cell activation through bivalent engagement and dimerization of T-cell receptors (TCRs). To monitor and control the level of unspecific T-cell activation, we developed a sensitive and quantitative T-cell-activation assay, which can detect aCD3 HD in TDB drug product by exploiting its ability to activate T cells in the absence of target cells. This assay provides in-vivo -relevant off-target T-cell-activation readout. Furthermore, we have demonstrated that this assay can serve as a platform assay for detecting T-cell-activating impurities across a broad spectrum of aCD3 bispecific molecules. It therefore has the potential to significantly benefit many T-cell-recruiting bispecific programs.