Discovery of antibodies and cognate surface targets for ovarian cancer by surface profiling.
Bärbel SchröfelbauerPatrick K KimesPaige HaukeCharlotte E ReidKevin ShaoSarah J HillRafael IrizarryWilliam C HahnPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Although antibodies targeting specific tumor-expressed antigens are the standard of care for some cancers, the identification of cancer-specific targets amenable to antibody binding has remained a bottleneck in development of new therapeutics. To overcome this challenge, we developed a high-throughput platform that allows for the unbiased, simultaneous discovery of antibodies and targets based on phenotypic binding profiles. Applying this platform to ovarian cancer, we identified a wide diversity of cancer targets including receptor tyrosine kinases, adhesion and migration proteins, proteases and proteins regulating angiogenesis in a single round of screening using genomics, flow cytometry, and mass spectrometry. In particular, we identified BCAM as a promising candidate for targeted therapy in high-grade serous ovarian cancers. More generally, this approach provides a rapid and flexible framework to identify cancer targets and antibodies.
Keyphrases
- high throughput
- high grade
- papillary thyroid
- flow cytometry
- single cell
- mass spectrometry
- small molecule
- squamous cell
- healthcare
- lymph node metastasis
- quality improvement
- binding protein
- palliative care
- escherichia coli
- drug delivery
- endothelial cells
- liquid chromatography
- high resolution
- dna binding
- cancer therapy
- ms ms
- staphylococcus aureus
- loop mediated isothermal amplification
- vascular endothelial growth factor
- wound healing