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Construction of Synthetic Phage Displayed Fab Library with Tailored Diversity
Published on: May 1, 2018
Antibody phage display libraries: contributions to oncology
Carmela Dantas-Barbosa1, Marcelo De Macedo Brigido2, Andrea Queiroz Maranhao2
1Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052-CNRS 5286, Centre Léon Bérard, Cheney D, 28 Rue Laënnec, 69373 Lyon Cedex 08, France.
Abstract:
Since the advent of phage display technology, dating back to 1985, antibody libraries displayed on filamentous phage surfaces have been used to identify specific binders for many different purposes, including the recognition of tumors. Phage display represents a high-throughput technique for screening billions of random fusion antibodies against virtually any target on the surface or inside cancer cells, or even soluble markers found in patient serum. Many phage display derived binders targeting important tumor markers have been identified. Selection directed to tumoral cells' surfaces lead to the identification of unknown tumoral markers. Also the improvement of methods that require smaller amounts of cells has opened the possibility to use this approach on patient samples. Robust techniques combining an antibody library displayed on the phage surface and protein microarray allowed the identification of auto antibodies recognized by patient sera. Many Ab molecules directly or indirectly targeting angiogenesis have been identified, and one of them, ramucirumab, has been tested in 27 phase I-III clinical trials in a broad array of cancers. Examples of such antibodies will be discussed here with emphasis on those used as probes for molecular imaging and other clinical trials.
Insights
Phage display technology identifies tumor-targeting antibodies for cancer research and clinical trials. This high-throughput method screens antibody libraries to find binders for tumor markers and angiogenesis, aiding in diagnostics and therapeutics.
Area of Science:
- Biotechnology
- Immunology
- Oncology
Background:
- Phage display technology, established in 1985, utilizes antibody libraries on phage surfaces for molecular recognition.
- This high-throughput screening method enables the identification of specific binders against diverse targets, including cancer cells and serum markers.
Purpose of the Study:
- To review the application of phage display technology in identifying tumor-targeting antibodies.
- To highlight antibodies used as probes for molecular imaging and in clinical trials for cancer treatment.
Main Methods:
- Screening of billions of random fusion antibodies against tumoral cells or soluble markers.
- Utilizing protein microarrays in conjunction with phage display for autoantibody identification in patient sera.
Main Results:
- Identification of numerous phage display-derived binders targeting key tumor markers and unknown tumoral antigens.
- Discovery of multiple antibody molecules targeting angiogenesis, with one (ramucirumab) progressing through extensive clinical trials.
Conclusions:
- Phage display is a powerful tool for discovering cancer-related antibodies, including diagnostic and therapeutic agents.
- Advancements in phage display methods facilitate the use of patient samples and the development of novel cancer therapies and imaging probes.
