ArticleBiomaterials2017
Liver specific gene immunotherapies resolve immune suppressive ectopic lymphoid structures of liver metastases and prolong survival.
Article in Biomaterials, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 56 citations in OpenAlex.
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- Nanoparticle Delivery of miR-122 Inhibits Colorectal Cancer Liver Metastasis.Cancer research · 2022Article
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- Two nanoformulations induce reactive oxygen species and immunogenetic cell death for synergistic chemo-immunotherapy eradicating colorectal cancer and hepatocellular carcinoma.Molecular cancer · 2021Article
- Article
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- Lipid nanoparticle technology for therapeutic gene regulation in the liver.Advanced drug delivery reviews · 2020Review
- Membrane-core nanoparticles for cancer nanomedicine.Advanced drug delivery reviews · 2020Review
- Liposomal Nanostructures for Drug Delivery in Gastrointestinal Cancers.The Journal of pharmacology and experimental therapeutics · 2019Review
- Relaxin gene delivery mitigates liver metastasis and synergizes with check point therapy.Nature communications · 2019Article
- Drug delivery systems targeting tumor-associated fibroblasts for cancer immunotherapy.Cancer letters · 2019Review
- Emerging Nano-/Microapproaches for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The ability to generate potent immunotherapies locally and transiently for the treatment of cancers is a promising strategy to improve efficacy and decrease off-target toxicities. Here, we explored an alternative approach for the delivery of immunotherapeutic agents, in which we deliver the pDNA of an engineered PD-L1 trap and/or CXCL12 trap to the nucleus of liver hepatocytes via a lipid calcium phosphate nanoparticle. This strategy greatly increased the concentrations of immunotherapeutic agents in the local tissue, allowing the therapy to inhibit the accumulation of immune suppressive cells and liver metastasis. Furthermore, we find that the lipid calcium phosphate nanoparticles containing the pCXCL12 trap resolved the formation of immune suppressive ectopic lymphoid structures, while the pPD-L1 trap promoted T-cell survival and migration into the liver following vaccination against tumor antigens (>180% increase in survival). This approach showed superior efficacy in the treatment of the liver metastasis compared to free protein immunotherapies. This strategy should be considered as an approach to support liver metastasis therapies as well as for future research interested in manipulating the chemokine/cytokine immune factors within the liver. SIGNIFICANCE: Our approach results in transient liver specific expression of gene immunotherapies with improved efficacy and reduced off-target toxicities over traditional systemically administered immunotherapies. This approach would allow clinicians to manipulate the liver and immune microenvironment to resist cancer invasion, improve organ health, and prolong patient survival.
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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.