Abstract
Phage display is a nanotechnology with limitless potential, first developed in 1985 and still awaiting to reach its peak. Awarded in 2018 with the Nobel Prize for Chemistry, the method allows the isolation of high-affinity ligands for diverse substrates, ranging from recombinant proteins to cells, organs, even whole organisms. Personalized therapeutic approaches, particularly in oncology, depend on the identification of new, unique, and functional targets that phage display, through its various declinations, can certainly provide. A fast-evolving branch in cancer research, immunotherapy is now experiencing a second youth after being overlooked for years; indeed, many reports support the concept of immunotherapy as the only non-surgical cure for cancer, at least in some settings. In this review, we describe literature reports on the application of peptide phage display to cancer immunotherapy. In particular, we discuss three main outcomes of this procedure: (i) phage display-derived peptides that mimic cancer antigens (mimotopes) and (ii) antigen-carrying phage particles, both as prophylactic and/or therapeutic vaccines, and (iii) phage display-derived peptides as small-molecule effectors of immune cell functions. Preclinical studies demonstrate the efficacy and vast potential of these nanosized tools, and their clinical application is on the way.
Highlights
The immune system changes and adapts during the progressive steps of tumorigenesis to recruit and activate all possible mechanisms of protection
When the TAA is presented on major histocompatibility complex (MHC) I, the complex is recognized by CD8+ cells that differentiate in cytotoxic T lymphocytes (CTLs) and kill cancer cells [3]
Despite the encouraging results summarized here, to our knowledge only one peptide derived from phage display screenings is as yet being investigated in clinical trials
Summary
The immune system changes and adapts during the progressive steps of tumorigenesis to recruit and activate all possible mechanisms of protection. A continuous and endogenous production of anti-TAA Abs would best serve the aim of achieving a therapeutic effect with the potential to eradicate the disease and prevent its recurrence for the rest of a patient’s life This second concept, known as active vaccination, was historically developed to combat pathogenic organisms but has been recently pursued in oncology. The third concept is a straightforward approach that has been defined “meddle with meddlers” [23], as in directly targeting the immune checkpoint inhibitors These three concepts have been applied to cancer treatment by means of different tools (e.g., peptides, Abs, aptamers, chemical molecules) developed with conventional techniques as discussed elsewhere [24,25,26].
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