Advancements in ovarian cancer immunodiagnostics and therapeutics via phage display technology

Abstract

Ovarian cancer, ranking as the seventh most prevalent malignancy among women globally, faces significant challenges in diagnosis and therapeutic intervention. The difficulties in early detection are amplified by the limitations and inefficacies inherent in current screening methodologies, highlighting a pressing need for more efficacious diagnostic and treatment strategies. Phage display technology emerges as a pivotal innovation in this context, utilizing extensive phage-peptide libraries to identify ligands with specificity for cancer cell markers, thus enabling precision-targeted therapeutic strategies. This technology promises a paradigm shift in ovarian cancer management, concentrating on targeted drug delivery systems to improve treatment accuracy and efficacy while minimizing adverse effects. Through a meticulous review, this paper evaluates the revolutionary potential of phage display in enhancing ovarian cancer therapy, representing a significant advancement in combating this challenging disease. Phage display technology is heralded as an essential instrument for developing effective immunodiagnostic and therapeutic approaches in ovarian cancer, facilitating early detection, precision-targeted medication, and the implementation of customized treatment plans.

Keywords: immunodiagnostics; ovarian cancer; personalized therapeutic strategies; phage display technology; targeted drug delivery.

Figure 1

Diverse Phage Types Exploited in Phage Display. Among them, filamentous M13 phages are prominent, along with “tail” phages like T7, λ, and T4, and compact ssRNA icosahedral phages MS2 and Qβ. Notably, key capsid proteins for peptides display are highlighted in red, phage families in black, genetic material in blue, and capsid dimensions in purple [adapted from (11)].

Figure 2

(A) Establishing the Phage Peptide Variant or Antibody Gene Library. Antibody libraries, fused with phage coat protein, are transformed into (E) coli. Enrichment of specific scFv-phage via target binding occurs, followed by removal of nonspecific or improperly folded scFvs through washing. Elution methods release specific scFv-phage fusions [adapted from (25)]. (B) Landscape Phage Concept: Illustrated is a distinct peptide “landscape” exhibited on the phage surface [adapted from (11)]. (C) Phage vector and selection: display valency is pivotal. Phage vectors carry recombinant genes for polyvalent display, while helper phages yield lower valence (typically pIII univalent) [adapted from (11)].

Figure 3

Phage selection. (A) In this process, a vast array of library variants is incorporated into phagemids, facilitating the transformation of (E) coli and subsequent phage rescue. The result is the creation of extensive phage libraries, which support the iterative biopanning process for the selection and isolation of phages that bind specifically to target antibodies. (B) The diagram illustrates Various Strategies for Harvesting High-Affinity Peptides Through Phage Display Screening: In situ screening involves the application of targets onto plates. Ex vivo screening is designated for isolating rare cells amidst heterogeneity. Screening using samples from human patients helps minimize species mismatches. In vitro screening is tailored to identify peptides specific to adherent cells, while organ-specific peptides are derived through in vivo biopanning and selection within living organisms [adapted from (50)]. (C) This is followed by further screening and sequencing of the identified phages, advancing towards the pinpointing of optimal target-specific ligands.

Figure 4

This illustration captures the process of ovarian cancer metastasis and the intricacies of its tumor microenvironment. It shows how ovarian cancer typically begins in the fallopian tube linings and spreads to the abdominal cavity. The diagram highlights the dynamic transitions between epithelial and mesenchymal states that are critical for the formation of secondary lesions. It further details the metabolic reprogramming within various cell types, including cancer and immune cells, contributing to a suppressive immune environment. This environment promotes tumor growth and progression by enhancing immunosuppression, facilitating robust cellular interactions, and enabling immune escape through a complex network of interconnected metabolites. [adapted from (57, 58)].

Figure 5

Innovations in Ovarian Cancer Immunodiagnostics and Therapeutic Strategies. This figure illustrates the critical role of serum biomarkers and nanosensors in diagnosing ovarian cancer, a condition typically managed through debulking surgery followed by systemic treatments like chemotherapy, targeted therapy, and immunotherapy. It highlights how conventional treatments modify the immune landscape, initially promoting immunosuppression for healing and subsequently enhancing immunostimulation to fight the disease. These dynamics underscore the importance of advancing immunotherapeutic strategies to maximize treatment effectiveness. [adapted from (78, 79)].

Figure 6

Phage Display Technology in Ovarian Cancer Treatment Customization. This diagram underscores the transformative role of phage display technology in ovarian cancer immunodiagnostics and therapy. It showcases how phage display facilitates the identification of specific ligands that target ovarian cancer cells, thus paving the way for innovative diagnostic and therapeutic approaches. This advancement enhances drug specificity and minimizes side effects, promising to revolutionize treatment modalities for ovarian cancer. [adapted from (57, 79)].