Towards Clinical Implementation of Adeno-Associated Virus (AAV) Vectors for Cancer Gene Therapy: Current Status and Future Perspectives

Hacker, Ulrich; Bentler, Martin; Kaniowska, Dorota; Morgan, Michael; Büning, Hildegard

doi:10.3390/cancers12071889

Cited by 52 publications

(47 citation statements)

References 196 publications

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“…Engineered AAV vectors are a promising gene delivery system due to their stability, strong safety profile, production scalability, and vector adaptability [ 123 ]. Moreover, the integration of a cancer-specific ligand on the surface of the viral capsid holds promise for the development of novel diagnostic and treatment modalities.…”

Section: Plectin-targeting Imaging Agents and Therapeuticsmentioning

confidence: 99%

Plectin in Cancer: From Biomarker to Therapeutic Target

Perez

Brinton²,

Kelly

2021

Cells

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The cytolinker and scaffolding protein, plectin, has emerged as a potent driver of malignant hallmarks in many human cancers due to its involvement in various cellular activities contributing to tumorigenesis, including cancer cell proliferation, adhesion, migration, invasion, and signal transduction. Evidence shows that beyond plectin’s diverse protein interactome, its cancer-specific mislocalization to the cell surface enables its function as a potent oncoprotein. As such, therapeutic targeting of plectin, its protein interactors, and, in particular, cancer-specific plectin (CSP) presents an attractive opportunity to impede carcinogenesis directly. Here, we report on plectin’s differential gene and protein expression in cancer, explore its mutational profile, and discuss the current understanding of plectin’s and CSP’s biological function in cancer. Moreover, we review the landscape of plectin as a prognostic marker, diagnostic biomarker, and target for imaging and therapeutic modalities. We highlight how, beyond their respective biological importance, plectin’s common overexpression in cancer and CSP’s cancer-specific bioavailability underscore their potential as high-value druggable targets. We discuss how recent evidence of the potent anti-cancer effects of CSP therapeutic targeting opens the door for cell-surface mislocalized proteins as novel therapeutic targets.

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Section: Plectin-targeting Imaging Agents and Therapeuticsmentioning

confidence: 99%

Plectin in Cancer: From Biomarker to Therapeutic Target

Perez

Brinton²,

Kelly

2021

Cells

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“…The approved applications of iron oxide nanoparticles include cancer diagnosis, cancer hyperthermia therapy, and iron deficiency anemia 53 . Moreover, AAV is also an approved gene vector for clinical use and now more and more gene therapies employ it for its safty 54 , 55 .…”

Section: Resultsmentioning

confidence: 99%

Gene interfered-ferroptosis therapy for cancers

2021

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Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis.

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“…One is the single injection of carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocyte, which is activated by AAV2-CEA-transduced dendritic cells, to treat patients with advanced gastric cancer (ClinicalTrials.gov Identifier: NCT02496273), and the other is AAV2-hAQP1 applied in patients with squamous cell head and neck cancer (ClinicalTrials.gov Identifier: NCT02602249). In the treatment of cancer diseases, AAV can transduce a large number of cancer cells and cancer stromal cells and stably express cancer therapeutic genes (suicide gene, immunostimulatory gene, cytotoxic gene, small interference (siRNA) and anti-angiogenesis gene) to inhibit cancer formation and progression [ 45 , 46 ]. The biggest problem with AAV-based cancer gene therapy is how to make AAV more specifically transduce to the cancer region [ 47 ].…”

Section: Aav Characteristics and Its Role In Cancer Gene Therapymentioning

confidence: 99%

Adeno‐associated virus (AAV)-based gene therapy for glioblastoma

Chen

Zhu

et al. 2021

Cancer Cell Int

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Glioblastoma (GBM) is the most common and malignant Grade IV primary craniocerebral tumor caused by glial cell carcinogenesis with an extremely poor median survival of 12–18 months. The current standard treatments for GBM, including surgical resection followed by chemotherapy and radiotherapy, fail to substantially prolong survival outcomes. Adeno-associated virus (AAV)-mediated gene therapy has recently attracted considerable interest because of its relatively low cytotoxicity, poor immunogenicity, broad tissue tropism, and long-term stable transgene expression. Furthermore, a range of gene therapy trials using AAV as vehicles are being investigated to thwart deadly GBM in mice models. At present, AAV is delivered to the brain by local injection, intracerebroventricular (ICV) injection, or systematic injection to treat experimental GBM mice model. In this review, we summarized the experimental trials of AAV-based gene therapy as GBM treatment and compared the advantages and disadvantages of different AAV injection approaches. We systematically introduced the prospect of the systematic injection of AAV as an approach for AAV-based gene therapy for GBM.

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Towards Clinical Implementation of Adeno-Associated Virus (AAV) Vectors for Cancer Gene Therapy: Current Status and Future Perspectives

Cited by 52 publications

References 196 publications

Plectin in Cancer: From Biomarker to Therapeutic Target

Plectin in Cancer: From Biomarker to Therapeutic Target

Gene interfered-ferroptosis therapy for cancers

Adeno‐associated virus (AAV)-based gene therapy for glioblastoma

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