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Scalable High Throughput Selection From Phage-displayed Synthetic Antibody Libraries
Published on: January 17, 2015
Progress on Phage Display Technology: Tailoring Antibodies for Cancer Immunotherapy
Renato Kaylan Alves França1,2, Igor Cabral Studart3,4, Marcus Rafael Lobo Bezerra3,4
1Molecular Immunology Laboratory, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, Brazil.
Abstract:
The search for innovative anti-cancer drugs remains a challenge. Over the past three decades, antibodies have emerged as an essential asset in successful cancer therapy. The major obstacle in developing anti-cancer antibodies is the need for non-immunogenic antibodies against human antigens. This unique requirement highlights a disadvantage to using traditional hybridoma technology and thus demands alternative approaches, such as humanizing murine monoclonal antibodies. To overcome these hurdles, human monoclonal antibodies can be obtained directly from Phage Display libraries, a groundbreaking tool for antibody selection. These libraries consist of genetically engineered viruses, or phages, which can exhibit antibody fragments, such as scFv or Fab on their capsid. This innovation allows the in vitro selection of novel molecules directed towards cancer antigens. As foreseen when Phage Display was first described, nowadays, several Phage Display-derived antibodies have entered clinical settings or are undergoing clinical evaluation. This comprehensive review unveils the remarkable progress in this field and the possibilities of using clever strategies for phage selection and tailoring the refinement of antibodies aimed at increasingly specific targets. Moreover, the use of selected antibodies in cutting-edge formats is discussed, such as CAR (chimeric antigen receptor) in CAR T-cell therapy or ADC (antibody drug conjugate), amplifying the spectrum of potential therapeutic avenues.
Insights
Phage display technology enables the direct selection of human monoclonal antibodies for cancer therapy, overcoming immunogenicity challenges. This innovative approach is advancing novel antibody-based treatments and drug conjugates.
Area of Science:
- Immunology
- Biotechnology
- Oncology
Background:
- Antibodies are crucial for cancer therapy, but developing non-immunogenic human antibodies is challenging.
- Traditional hybridoma technology has limitations for generating human anti-cancer antibodies.
- Phage display offers an alternative for selecting human antibodies against specific cancer targets.
Purpose of the Study:
- To review the progress and strategies in using phage display for anti-cancer antibody development.
- To highlight the potential of phage display-derived antibodies in various therapeutic formats.
- To discuss advancements in antibody selection and refinement for targeted cancer therapies.
Main Methods:
- Utilizing genetically engineered phages in libraries to display antibody fragments (scFv, Fab).
- In vitro selection of novel antibody molecules directed against cancer antigens.
- Reviewing clinical progression and evaluation of phage display-derived antibodies.
Main Results:
- Phage display facilitates the selection of human monoclonal antibodies, bypassing immunogenicity issues.
- Several phage display-derived antibodies are now in clinical trials or evaluation.
- Advanced antibody formats like CAR T-cell therapy and antibody-drug conjugates are being developed.
Conclusions:
- Phage display is a powerful tool for generating targeted anti-cancer antibodies.
- This technology enables the development of novel therapeutic strategies, including antibody-drug conjugates and CAR T-cell therapies.
- Continued innovation in phage selection and antibody refinement promises expanded therapeutic options for cancer patients.
