Comparative characterization of different molecular formats of bispecific antibodies targeting EGFR and PD-L1
Mohan, N. et al. (2022) Comparative characterization of different molecular formats of bispecific antibodies targeting EGFR and PD-L1. Pharmaceutics 14, 1381. DOI: 10.3390/pharmaceutics14071381
Programmed death-ligand 1 (PD-L1), an immune checkpoint protein, is overexpressed in triple-negative breast cancers (TNBC). TNBC is characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2). Bispecific antibodies that can simultaneously target two different antigens offer new therapeutic modalities to treat cancer, but they can be challenging to characterize.
The researchers generated two formats of IgG1-like bispecific antibodies targeting the same antigens, EGFR and PD-L1. They used the CellTiter-Glo® assay to investigate the potency of these antibody formats in TNBC cell model systems. With the PD-1/PD-L1 Blockade Bioassay, they showed that both antibody formats could disrupt the engagement of PD-1 to its ligand PD-L1, promoting TCR signaling, transcriptional activation and cytokine production. Further, the researchers demonstrated that one of the antibody formats induced potent ADCC activity in high-EGFR-expressing cells, using the ADCC Reporter Bioassay. They conclude that selection of appropriate cell lines and assays is critically important for assay development and potency testing of bispecific antibodies.
Keywords: bispecific antibodies, EFGR, PD-L1, triple-negative breast cancer (TNBC), bioassays
