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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.
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http://dx.doi.org/10.3390/molecules25040843 | DOI Listing |
Haematologica
September 2025
Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel.
We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a high-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors.
View Article and Find Full Text PDFHaematologica
September 2025
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD,.
Immunotherapies, including cell therapies, are effective anti-cancer agents. However, cellular product persistence can be limiting with short functional duration of activity contributing to disease relapse. A variety of manufacturing protocols are used to generate therapeutic engineered T-cells; these differ in techniques used for T-cell isolation, activation, genetic modification, and other methodology.
View Article and Find Full Text PDFFuture Oncol
September 2025
Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China.
Immune checkpoint therapy has demonstrated significant potential in the treatment of various solid tumors. Among these, tumor-induced immunosuppression mediated by programmed cell death protein 1 (PD-1) represents a critical checkpoint. PD-1/programmed death-ligand 1 (PD-L1) inhibitors have been proven to exhibit substantial efficacy in solid tumors such as melanoma and bladder cancer.
View Article and Find Full Text PDFAnn Palliat Med
September 2025
Brown University Health Cancer Institute, Providence, RI, USA; Division of Geriatrics and Palliative Medicine, Department of Medicine, Alpert Medical School of Brown University, Providence, RI, US.
ancreatic cancer is an aggressive disease and often presents at an advanced stage with no curative options. The disease is often characterized by rapid progression, limited or short-lived responsiveness to standard therapies, and a profound impact on patients' quality of life. Despite advances in targeted therapies and immunotherapy, curative outcomes remain elusive for the majority of patients with advanced or high-grade disease with a 5-year survival rate of less than 10%.
View Article and Find Full Text PDFMol Ther
September 2025
Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, partly due to cancer stem cells (CSCs) that drive progression and treatment resistance. We explored the therapeutic potential of inducing cuproptosis, a copper-dependent regulated cell death, in CSC-enriched PDAC models. Using human and murine PDAC models, we evaluated elesclomol, a copper transport enhancer.
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