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

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2025 Jan 8

PMID 39772164

Authors

Nusa Brisar

Katja Suster

Andrej Cor

Affiliations

Soon will be listed here.

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.

References

Faix P, Burg M, Gonzales M, Ravey E, Baird A, LaRocca D . Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection. Biotechniques. 2004; 36(6):1018-22, 1024, 1026-9. DOI: 10.2144/04366RR03. View

de Vries C, Chen Q, Demirdjian S, Kaber G, Khosravi A, Liu D . Phages in vaccine design and immunity; mechanisms and mysteries. Curr Opin Biotechnol. 2020; 68:160-165. PMC: 8137517. DOI: 10.1016/j.copbio.2020.11.002. View

Aghebati-Maleki L, Bakhshinejad B, Baradaran B, Motallebnezhad M, Aghebati-Maleki A, Nickho H . Phage display as a promising approach for vaccine development. J Biomed Sci. 2016; 23(1):66. PMC: 5041315. DOI: 10.1186/s12929-016-0285-9. View

Bittner C, Grassau B, Frenzel K, Baur X . Identification of wheat gliadins as an allergen family related to baker's asthma. J Allergy Clin Immunol. 2007; 121(3):744-9. DOI: 10.1016/j.jaci.2007.09.051. View

Jestin J, Volioti G, Winter G . Improving the display of proteins on filamentous phage. Res Microbiol. 2001; 152(2):187-91. DOI: 10.1016/s0923-2508(01)01191-3. View

Pulido J, Kottke T, Thompson J, Galivo F, Wongthida P, Diaz R . Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma. Nat Biotechnol. 2012; 30(4):337-43. PMC: 3891505. DOI: 10.1038/nbt.2157. View

Li G, Ali S, McArdle S, Mian S, Ahmad M, Miles A . Immunity to tumour antigens. Curr Pharm Des. 2005; 11(27):3501-9. DOI: 10.2174/138161205774414583. View

Rakonjac J, Russel M, Khanum S, Brooke S, Rajic M . Filamentous Phage: Structure and Biology. Adv Exp Med Biol. 2018; 1053:1-20. DOI: 10.1007/978-3-319-72077-7_1. View

Li G, Miles A, Line A, Rees R . Identification of tumour antigens by serological analysis of cDNA expression cloning. Cancer Immunol Immunother. 2004; 53(3):139-43. PMC: 11032928. DOI: 10.1007/s00262-003-0471-y. View

10.

Shoae-Hassani A, Mortazavi-Tabatabaei S, Sharif S, Madadi S, Rezaei-Khaligh H, Verdi J . Recombinant λ bacteriophage displaying nanobody towards third domain of HER-2 epitope inhibits proliferation of breast carcinoma SKBR-3 cell line. Arch Immunol Ther Exp (Warsz). 2012; 61(1):75-83. DOI: 10.1007/s00005-012-0206-x. View

11.

Crameri R, Scheurer S, Vieths S, Becker W . Patient-tailored cloning of allergens by phage display: peanut (Arachis hypogaea) profilin, a food allergen derived from a rare mRNA. J Chromatogr B Biomed Sci Appl. 2001; 756(1-2):295-305. DOI: 10.1016/s0378-4347(01)00088-3. View

12.

Nemudraya A, Richter V, Kuligina E . Phage Peptide Libraries As a Source of Targeted Ligands. Acta Naturae. 2016; 8(1):48-57. PMC: 4837571. View

13.

Natale P, Bruser T, Driessen A . Sec- and Tat-mediated protein secretion across the bacterial cytoplasmic membrane--distinct translocases and mechanisms. Biochim Biophys Acta. 2007; 1778(9):1735-56. DOI: 10.1016/j.bbamem.2007.07.015. View

14.

Hufton S, Moerkerk P, Meulemans E, de Bruine A, Arends J, Hoogenboom H . Phage display of cDNA repertoires: the pVI display system and its applications for the selection of immunogenic ligands. J Immunol Methods. 2000; 231(1-2):39-51. DOI: 10.1016/s0022-1759(99)00139-8. View

15.

Eriksson T, Rasool O, Huecas S, Whitley P, Crameri R, Appenzeller U . Cloning of three new allergens from the dust mite Lepidoglyphus destructor using phage surface display technology. Eur J Biochem. 2001; 268(2):287-94. DOI: 10.1046/j.1432-1327.2001.01879.x. View

16.

Carcamo J, Ravera M, Brissette R, Dedova O, Beasley J, Wan C . Unexpected frameshifts from gene to expressed protein in a phage-displayed peptide library. Proc Natl Acad Sci U S A. 1998; 95(19):11146-51. PMC: 21610. DOI: 10.1073/pnas.95.19.11146. View

17.

Zhang D, Huang J, Li W, Zhang Z, Zhu M, Feng Y . Screening and identification of a CD44v6 specific peptide using improved phage display for gastric cancer targeting. Ann Transl Med. 2020; 8(21):1442. PMC: 7723568. DOI: 10.21037/atm-19-4781. View

18.

Yau A, Chu S, Yap W, Wong C, Chia A, Tang Y . Phage display screening in breast cancer: From peptide discovery to clinical applications. Life Sci. 2024; 357:123077. DOI: 10.1016/j.lfs.2024.123077. View

19.

Ferreira A, Lamy M, Margarida Rocha M, Silva G, Bandeiras T, Barbas A . Production and characterization of a novel Delta-like 1 functional unit as a tool for Notch pathway activation and generation of a specific antibody. Protein Expr Purif. 2018; 146:8-16. DOI: 10.1016/j.pep.2018.01.008. View

20.

Saw P, Song E . Phage display screening of therapeutic peptide for cancer targeting and therapy. Protein Cell. 2019; 10(11):787-807. PMC: 6834755. DOI: 10.1007/s13238-019-0639-7. View