ArticleProceedings of the National Academy of Sciences of the United States of America2016
AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
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- Transmorphic phage-guided systemic delivery of TNFα gene for the treatment of human pediatric medulloblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Review
- MEN1 promotes ferroptosis by inhibiting mTOR-SCD1 axis in pancreatic neuroendocrine tumors.Acta biochimica et biophysica Sinica · 2022Article
- Bacteriophage-Mediated Cancer Gene Therapy.International journal of molecular sciences · 2022Review
- Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles.EMBO molecular medicine · 2022Article
- Development of anti-somatostatin receptors CAR T cells for treatment of neuroendocrine tumors.Journal for immunotherapy of cancer · 2022Article
- Best of most possible worlds: Hybrid gene therapy vectors based on parvoviruses and heterologous viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Delivery of cancer therapies by synthetic and bio-inspired nanovectors.Molecular cancer · 2021Review
- Design and proof-of-concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.bioRxiv : the preprint server for biology · 2021Article
- Multiple Endocrine Neoplasia Type 1: Latest Insights.Endocrine reviews · 2021Review
- Bacteriophages as Therapeutic and Diagnostic Vehicles in Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- B7 immune-checkpoints as targets for the treatment of neuroendocrine tumors.Endocrine-related cancer · 2021Article
- Doxorubicin Improves Cancer Cell Targeting by Filamentous Phage Gene Delivery Vectors.International journal of molecular sciences · 2020Article
- Initial Steps for the Development of a Phage-Mediated Gene Replacement Therapy Using CRISPR-Cas9 Technology.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived. Here we designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor (TNF) transgene specifically to NETs. These functional attributes of AAVP-TNF particles displaying the octreotide peptide motif (termed Oct-AAVP-TNF) were confirmed in vitro, in SSTR type 2-expressing NET cells, and in vivo using cohorts of pancreatic NET-bearing Men1 tumor-suppressor gene KO mice, a transgenic model of functioning (i.e., insulin-secreting) tumors that genetically and clinically recapitulates the human disease. Finally, preclinical imaging and therapeutic experiments with pancreatic NET-bearing mice demonstrated that Oct-AAVP-TNF lowered tumor metabolism and insulin secretion, reduced tumor size, and improved mouse survival. Taken together, these proof-of-concept results establish Oct-AAVP-TNF as a strong therapeutic candidate for patients with NETs of the pancreas. More broadly, the demonstration that a known, short, biologically active motif can direct tumor targeting and receptor-mediated internalization of AAVP particles may streamline the potential utility of myriad other short peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers and perhaps many nonmalignant diseases as well.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.