Preparation of Phage Display cDNA Libraries for Identifying Immunogenic Tumor Antigens: Challenges in Functional cDNA Presentation and Approaches to Overcoming Them

Abstract

Cancer continues to represent a substantial burden in terms of its morbidity and mortality, underscoring the imperative for the development of novel and efficacious treatment modalities. Recent advances in cancer immunotherapy have highlighted the importance of identifying tumour-specific antigens, which can assist the immune system in targeting malignant cells effectively. Phage display technology has emerged as an effective tool for the discovery of novel antigens through cDNA library screening, representing a significant advancement in the field of immunological research. This review examines the discovery of tumour antigens using phage display technology, emphasising the construction of cDNA libraries, their subsequent display on bacteriophages and the utilisation of diverse biopanning techniques. These elements play a pivotal role in advancing the discovery of novel tumour antigens and the development of targeted cancer therapies. This review addresses the challenges associated with the filamentous phage display of cDNA libraries and proposes strategies to improve the effectiveness of this approach, encouraging further research for clinical applications.

Keywords: biopanning; cDNA libraries; filamentous bacteriophages; immunotherapy; nanoparticles; phage display technology; tumor antigens.

Figure 1

Schematic representation of the construction of cDNA libraries and their display on filamentous bacteriophages.

Figure 2

Schematic of an affinity-driven process in which phage-displayed libraries are screened against a variety of targets and target-specific phage-displayed (poly)peptides (e.g., novel cancer ligands) are subsequently identified.

Figure 3

Indirect fusion to pIII coat proteins. Adapted from [47].