Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 120, Issue 1, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2206751120
Keywords
phage display; antibody discovery; cancer surface targets
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In this study, a high-throughput platform was developed to simultaneously discover antibodies and cancer-specific targets based on phenotypic binding profiles. Utilizing genomics, flow cytometry, and mass spectrometry, a wide diversity of cancer targets including receptor tyrosine kinases, adhesion and migration proteins, proteases, and proteins regulating angiogenesis were identified in ovarian cancer. BCAM was identified as a promising candidate for targeted therapy in high-grade serous ovarian cancers. Overall, this approach provides a rapid and flexible framework to identify cancer targets and antibodies.
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.
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