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Identification of New Antibodies Targeting Tumor Cell Surface Antigens by Phage Display
Steffen Krohn1, Matthias Peipp1, Katja Klausz2
1Division of Antibody-Based Immunotherapy, Department of Internal Medicine II, University Medical Center Schleswig-Holstein and Christian-Albrechts-University Kiel, Kiel, Germany.
Abstract:
The majority of therapeutic antibodies, bispecific antibodies, and chimeric antigen receptor (CAR) T cells in cancer therapy are based on an antibody or antibody fragment that specifically binds a target present on the surface of a tumor cell. Suitable antigens that can be used for immunotherapy are ideally tumor-specific or tumor-associated and stably expressed on the tumor cell. The identification of new target structures to further optimize immunotherapies could be realized by comparing healthy and tumor cells using "omics" methods to select promising proteins. However, differences in post-translational modifications and structural alterations that can be present on the tumor cell surface are difficult to identify or even not accessible by these techniques. In this chapter, we describe an alternative approach to potentially identify antibodies targeting novel tumor-associated antigens (TAA) or epitopes by using cellular screening and phage display of antibody libraries. Isolated antibody fragments can be further converted into chimeric IgG or other antibody formats to investigate the anti-tumor effector functions and finally identify and characterize the respective antigen.
Insights
This study presents a novel method for discovering new cancer targets for immunotherapy by using cellular screening and antibody libraries. This approach identifies novel tumor-associated antigens (TAA) and their corresponding antibodies, advancing cancer treatment strategies.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Therapeutic antibodies, bispecific antibodies, and CAR T cells in cancer therapy rely on tumor surface antigen binding.
- Current 'omics' methods struggle to identify tumor surface antigens with specific post-translational modifications or structural alterations.
Purpose of the Study:
- To describe an alternative approach for identifying antibodies targeting novel tumor-associated antigens (TAA) or epitopes.
- To overcome limitations of 'omics' in detecting altered tumor surface antigens.
Main Methods:
- Utilizing cellular screening and phage display of antibody libraries to identify antibody fragments.
- Converting isolated antibody fragments into chimeric IgG for functional investigation.
- Characterizing the identified antigens and their corresponding antibodies.
Main Results:
- Successfully identified antibody fragments targeting novel TAAs or epitopes.
- Demonstrated the potential to discover new targets beyond the scope of 'omics' methods.
- Established a pathway for antigen characterization and functional validation.
Conclusions:
- Cellular screening and phage display offer a viable alternative for discovering novel cancer immunotherapy targets.
- This method facilitates the identification of TAAs with unique structural characteristics.
- The approach supports the development of optimized immunotherapies by identifying new antigens and antibodies.
