Phage Display in Cancer Research

Dear Colleagues,

The fascinating story of the miracle recovery of a cervical cancer patient vaccinated with a live attenuated rabies virus, along with many other successful cases of using viruses observed after 1904, was reported by Ma et all.¹ Virotherapy was intensively studied in the mid twentieth century, when researchers treated cancer patients with a wide range of oncolytic viruses (OVs) which demonstrated ability to selectively bind to and kill tumor cells. However, despite their great promise, very few virotherapies reached clinical trials. In the late 1970s, recombinant technology enabled the modification of wild-type viruses to produce safer and more effective virus strains. The subsequent successful use of recombinant OVs for cancer treatment stimulated development of novel viral-based platforms, such as virus-like particles (VLPs), which are assembled from native viral proteins and normally inherit the tropism of the virus from which they originate. The absence of natural tropism towards mammalian cells is a great advantage in the engineering of bacteriophages as drug and gene delivery vectors precisely targeted to cancer cell receptors.^{2, 3} The idea behind employing the recombinant phages in antitumor therapy is their ability to target the tumor-specific antigens in a polyvalent fashion that allows strong specific and selective binding of phage-based vehicles to cancer cells, and delivery of their toxic cargo to targeted cellular compartments.⁴ Examples of phage display applications in oncology, cell biology, drug discovery, and delivery systems have been formally reviewed.^{5, 6}

As noted above, filamentous and other types of bacteriophages, commonly used in phage display, have no natural tropism to mammalian cells and are not considered as killers of tumors, but they serve as suitable vectors for generating random protein phage-displayed libraries — a rich source of ligands for mammalian cell receptors including cancer-specific receptors.⁷ A spectacular chronicle of pharmaceutical antibody development using phage display was recounted by Sir Gregory P. Winter in his Nobel lecture.⁸

This Special Issue aims to demonstrate the power of phage display as a universal tool of directed molecular evolution in cancer research. We call for manuscripts that bring the fundamental principles of phage display and directed evolution to a new level in the development of diagnostics and chemotherapy for cancer diseases. For example, combining affinity selection with natural functional selection in vivo allows the creation of novel proteins and protein-based (nano)materials with unique emergent properties, which are used as artificial regulators of inter- and intracellular processes in tumor tissues and cancer cells, and novel (nano)materials for medicine, science, and technology.

References:

[1] Ma, X. Y., Hill, B. D., Hoang, T., and Wen, F. (2022) Virus-inspired strategies for cancer therapy, Seminars in Cancer Biology 86, 1143–1157.

[2] Petrenko, V. A. (2018) Landscape Phage: Evolution from Phage Display to Nanobiotechnology, Viruses-Basel 10.

[3] Petrov, G., Dymova, M., and Richter, V. (2022) Bacteriophage-Mediated Cancer Gene Therapy, Int J Mol Sci 23.

[4] Petrenko, V. A., and Gillespie, J. W. (2017) Paradigm shift in bacteriophage-mediated delivery of anticancer drugs: from targeted "magic bullets' to self-navigated "magic missiles', Expert Opinion on Drug Delivery 14, 373–384.

[5] Zambrano-Mila, M. S., Blacio, K. E. S., and Vispo, N. S. (2020) Peptide Phage Display: Molecular Principles and Biomedical Applications, Therapeutic Innovation & Regulatory Science 54, 308–317.

[6] Manivannan, A. C., Dhandapani, R., Velmurugan, P., Thangavelu, S., Paramasivam, R., Ragunathan, L., and Saravanan, M. (2022) Phage in cancer treatment – Biology of therapeutic phage and screening of tumor targeting peptide, Expert Opinion on Drug Delivery 19, 873–882.

[7] Smith, G. P. (2019) Phage Display: Simple Evolution in a Petri Dish (Nobel Lecture), Angew Chem Int Ed Engl 58, 14428–14437.

[8] Nagano, K., and Tsutsumi, Y. (2021) Phage Display Technology as a Powerful Platform for Antibody Drug Discovery, Viruses 13, 178.

[9] Sir Gregory P. Winter: Nobel Lecture in Chemistry 2018 - YouTube.

Prof. Dr. Valery A. Petrenko
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.