Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma

Iwagami, Yoshifumi; Casulli, Sarah; Nonomura, Katsuya; Kim, Miran; Carlson, Richard P.; Ogawa, Kosuke; Lebowitz, Michael; Fuller, Steven A.; Biswas, Biswajit; Stewart, Solomon; Dong, Xiaoqun; Ghanbari, Hossein; Wands, Jack R.

doi:10.1016/j.heliyon.2017.e00407

Cited by 27 publications

(45 citation statements)

References 47 publications

(68 reference statements)

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“…The next anti-ASPH vaccine was based on a bacteriophage lambda display system. The viral capsid protein gpD was fused with the N-or C-terminus of ASPH and immunogenicity of these nanoparticle-forming constructs was verified in two mouse tumor models [99]. The vaccine PAN-301-1 containing these constructs has already been examined in a phase 1 clinical trial in 12 patients with biochemically relapsed prostate cancer [100].…”

Section: Small Molecule Inhibitorsmentioning

confidence: 99%

Aspartate β-hydroxylase as a target for cancer therapy

Kanwal

Šmahel

Olsen

et al. 2020

J Exp Clin Cancer Res

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As metastasis is a major cause of death in cancer patients, new anti-metastatic strategies are needed to improve cancer therapy outcomes. Numerous pathways have been shown to contribute to migration and invasion of malignant tumors. Aspartate β-hydroxylase (ASPH) is a key player in the malignant transformation of solid tumors by enhancing cell proliferation, migration, and invasion. ASPH also promotes tumor growth by stimulation of angiogenesis and immunosuppression. These effects are mainly achieved via the activation of Notch and SRC signaling pathways. ASPH expression is upregulated by growth factors and hypoxia in different human tumors and its inactivation may have broad clinical impact. Therefore, small molecule inhibitors of ASPH enzymatic activity have been developed and their anti-metastatic effect confirmed in preclinical mouse models. ASPH can also be targeted by monoclonal antibodies and has also been used as a tumor-associated antigen to induce both cluster of differentiation (CD) 8 + and CD4 + T cells in mice. The PAN-301-1 vaccine against ASPH has already been tested in a phase 1 clinical trial in patients with prostate cancer. In summary, ASPH is a promising target for anti-tumor and anti-metastatic therapy based on inactivation of catalytic activity and/or immunotherapy.

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Section: Small Molecule Inhibitorsmentioning

confidence: 99%

Aspartate β-hydroxylase as a target for cancer therapy

Kanwal

Šmahel

Olsen

et al. 2020

J Exp Clin Cancer Res

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“…3 ) ( 52 ). λ phage nanoparticles expressing human AspH-derived proteins and AspH protein-loaded dendritic cells (DCs) migrate from the blood to lymph nodes to activate antigen specific CD4 + and CD8 + T cells; subsequently, T helper (Th)1 and Th2 immune responses are induced to promote lymphocytic infiltration and widespread necrosis in tumors ( 52 , 53 ).…”

Section: Molecular Functions Of Asph In Cancermentioning

confidence: 99%

“…In mouse models, high levels of AspH induced more aggressive tumors, characterized by rapid growth and extensive metastases ( 32 ). Notably, phage vaccination markedly decreased pulmonary metastasis and enhanced survival in the 4T1 breast cancer model (with AspH overexpression) ( 53 ). On the other hand, in estrogen receptor-positive breast cancer cells, the activation of MAPK and PI3K cascades upregulates AspH mRNA expression when tamoxifen sensitivity is decreased ( 84 ).…”

Section: Asph Expression In Various Types Of Cancermentioning

confidence: 99%

Diverse molecular functions of aspartate β‑hydroxylase in cancer (Review)

Zheng

Wang

et al. 2020

Oncol Rep

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Aspartate/asparagine β-hydroxylase (AspH) is a type II transmembrane protein that catalyzes the post-translational hydroxylation of definite aspartyl and asparaginyl residues in epidermal growth factor-like domains of substrates. In the last few decades, accumulating evidence has indicated that AspH expression is upregulated in numerous types of human malignant cancer and is associated with poor survival and prognosis. The AspH protein aggregates on the surface of tumor cells, which contributes to inducing tumor cell migration, infiltration and metastasis. However, small-molecule inhibitors targeting hydroxylase activity can markedly block these processes, both in vitro and in vivo . Immunization of tumor-bearing mice with a phage vaccine fused with the AspH protein can substantially delay tumor growth and progression. Additionally, AspH antigen-specific CD4 + and CD8 + T cells were identified in the spleen of tumor-bearing mice. Therefore, these agents may be used as novel strategies for cancer treatment. The present review summarizes the current progress on the underlying mechanisms of AspH expression in cancer development.

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“…As mentioned earlier, ligand density influences the type of immune response that develops and is of particular importance to response to cancer therapeutics. 82 Phage display vaccines have been targeted toward cancers such as breast, 83,84 liver, 85 and lung, 86 and some examples are discussed below in detail.…”

Section: Phage As a Tumor Antigen Display Toolmentioning

confidence: 99%

Phage display as a tool for vaccine and immunotherapy development

Hess

Jewell

2019

Bioengineering & Transla Med

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Bacteriophages, or phages, are viruses that specifically infect bacteria and coopt the cellular machinery to create more phage proteins, eventually resulting in the release of new phage particles. Phages are heavily utilized in bioengineering for applications ranging from tissue engineering scaffolds to immune signal delivery. Of specific interest to vaccines and immunotherapies, phages have demonstrated an ability to activate both the innate and adaptive immune systems. The genome of these viral particles can be harnessed for DNA vaccination, or the surface proteins can be exploited for antigen display. More specifically, genes that encode an antigen of interest can be spliced into the phage genome, allowing antigenic proteins or peptides to be displayed by fusion to phage capsid proteins. Phages therefore present antigens to immune cells in a highly ordered and repetitive manner. This review discusses the use of phage with adjuvanting activity as antigen delivery vehicles for vaccination against infectious disease and cancer. K E Y W O R D S bacteriophage, biomaterials, drug delivery, immunology, nanotechnology, phage display, vaccine 1 | INTRODUCTION Bacteriophages, or phages, are prokaryotic viruses that specifically infect bacteria, and are the most abundant life form on earth. 1 Phages were first discovered in the early 20th century and noted for their antibacterial activity. The practice of administering phages (i.e., phage therapy) to patients suffering from bacterial infections began shortly after their discovery, but was controversial largely due to lack of mechanistic knowledge and variable success rates. In fact, the treatment was largely abandoned upon the discovery of antibiotics. 2 Research in this field was reenergized, however, following the development of phage display systems in 1985. 3 George Smith, a chemist at the University of Missouri, demonstrated fusion of peptides to the outer (i.e., capsid) proteins of phages enabling surface display. This work, for which Smith shared a Nobel Prize in 2018, laid the ground work for affinity selection, epitope mapping, and antibody discovery. Since this time, phages have been an important tool for the bioengineering field, exploited for a range of applications including theranostics, 4 batteries, 5,6 drug delivery, 7 and vaccine development. 1Phages are one of many nanotechnologies being investigated for these applications. This review will focus on the advantages that phages provide to the nanomedicine field, specifically vaccination and immunotherapy. Nanomedicine ranges from diagnostics to treatments and relies on the fields of biomedical and chemical engineering,

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Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma

Cited by 27 publications

References 47 publications

Aspartate β-hydroxylase as a target for cancer therapy

Aspartate β-hydroxylase as a target for cancer therapy

Diverse molecular functions of aspartate β‑hydroxylase in cancer (Review)

Phage display as a tool for vaccine and immunotherapy development

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