Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-β gene and poly I: poly C in a murine lung metastasis model

Sakurai, Fuminori; Terada, T.; Maruyama, Masato; Watanabe, Yoshihiko; Yamashita, Fumiyoshi; Takakura, Yoshinobu; Hashida, Mitsuru

doi:10.1038/sj.cgt.7700617

Cited by 47 publications

(24 citation statements)

References 51 publications

(60 reference statements)

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“…In fact, even mammalian DNA becomes a potent immune stimulant when combined with cationic liposomes, as demonstrated recently in a murine tumor model (34). Moreover, cationic liposomes can be used to potentiate immune activation by other TLR agonists, including the TLR3 agonist polyI:C and TLR7/8 agonists such as single-stranded RNA (35)(36)(37)(38).…”

Section: Liposomes Enhance Innate Immune Activation By Nucleic Acidsmentioning

confidence: 96%

Liposome–nucleic acid immunotherapeutics

Dow¹

2007

Expert Opinion on Drug Delivery

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Cationic liposome-nucleic acid complexes, which were originally developed for use as non-viral gene delivery vectors, may now have an equally important application as immunotherapeutic drugs. Recent studies have highlighted the ability of cationic liposomes to markedly potentiate activation of the innate immune system by certain Toll-like receptor (TLR) agonists. The immune enhancing properties of cationic liposomes are most obvious when they are combined with nucleic acid agonists for endosomally-located TLRs, including TLR3, TLR7/8, and TLR9. How this immune potentiation by cationic liposomes is mediated is not completely understood, but is thought to reflect the combined effects of more efficient endosomal targeting, protection from extracellular degradation, and signaling through newly identified cytoplasmic receptors for nucleic acids. The potent innate immune stimulatory properties of liposome-nucleic acid complexes make them particularly effective as immunotherapeutics or vaccine adjuvants. As stand-alone immunotherapeutics, liposome-nucleic acid complexes have demonstrated impressive anti-cancer activity in a number of different animal tumor models. Moreover, liposome-nucleic acid complexes also show promise for immunotherapy of acute viral and bacterial infections and chronic fungal infections. When used as vaccine adjuvants, liposome-nucleic acid complexes target antigens for efficient uptake by dendritic cells and are particularly effective in eliciting T cell responses. Thus, cationic liposomes combined with nucleic acids form the basis for a potent and versatile immunotherapeutic platform.

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Section: Liposomes Enhance Innate Immune Activation By Nucleic Acidsmentioning

confidence: 96%

Liposome–nucleic acid immunotherapeutics

Dow¹

2007

Expert Opinion on Drug Delivery

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“…Using these gene expression characteristics of the lung, lipoplex was applied to the prevention of lung cancer metastasis in mice. 68,69) Since the physicochemical properties of pDNA are almost the same, irrespective of the encoding cDNA for the therapy, targeting technologies are especially required for their broad clinical application.…”

Section: Cationic Liposomes For Gene Delivery Following the Systemic mentioning

confidence: 99%

Lipid Carrier Systems for Targeted Drug and Gene Delivery

2005

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For effective chemotherapy, it is necessary to deliver therapeutic agents selectively to their target sites, since most drugs are associated with both beneficial effects and side effects. The use of lipid dispersion carrier systems, such as lipid emulsions and liposomes, as carriers of lipophilic drugs has attracted particular interest. A drug delivery system can be defined as a methodology for manipulating drug distribution in the body. Since drug distribution depends on the carrier, administration route, particle size of the carrier, lipid composition of the carrier, electric charge of the carrier and ligand density of the targeting carrier, these factors must be optimized. Recently, the lipid carrier system has also been applied to gene delivery systems for gene therapy. However, in both drug and gene medicine cases, a lack of cell-selectivity limits the wide application of this kind of drug and/or gene therapy. Therefore, lipid carrier systems for targeted drug and gene delivery must be developed for the rational therapy. In this review, we shall focus on the progress of research into lipid carrier systems for drug and gene delivery following systemic or local injection.

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“…13 Bauerschmitz et al 14 showed that modified adenovirus was more efficient than native virus at impeding growth of tumors. Additionally, Sakurai et al 15 showed systemic, i.v. delivery of IFNb or IFNg lipoplexes to be effective prophylactically as well as therapeutically against colon carcinoma lung metastases.…”

Section: Introductionmentioning

confidence: 99%

Targeting of products of genes to tumor sites using adoptively transferred A-NK and T-LAK cells

et al. 2007

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Despite successes in animals, cytokine gene expression selectively in human tumors is difficult to achieve owing to lack of efficient delivery methods. Since interleukin (IL)-2-activated natural killer (A-NK) and phytohemagglutinin and IL-2 activated killer T (T-LAK) cells, as previously demonstrated, localize and accumulate in murine lung tumor metastases following adoptive transfer, we transduced them to test their ability to deliver products of genes selectively to tumors. Assessments of transduction efficiency in vitro demonstrated that adenoviral transduction consistently resulted in high (460%) transduction rates and substantial expression of transgenes such as GFP, Red2, luciferase, b-galactosidase and mIL-12 for at least 4 days. In vivo experiments illustrated that Ad-GFP transduced A-NK and Ad-Red2 (RFP) transduced T-LAK or mIL-12 transduced A-NK cells localized 10-50-fold more or survived significantly better than mock transduced cells, respectively, within lung metastases than in the surrounding normal lung tissue. Most importantly, mIL-12 transduced A-NK cells provided a significantly greater antitumor response than non-transduced A-NK cells. Thus, adoptive transfer of A-NK and T-LAK cells represents an efficient method for targeting products of genes to tumor sites.

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Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-β gene and poly I: poly C in a murine lung metastasis model

Cited by 47 publications

References 51 publications

Liposome–nucleic acid immunotherapeutics

Liposome–nucleic acid immunotherapeutics

Lipid Carrier Systems for Targeted Drug and Gene Delivery

Targeting of products of genes to tumor sites using adoptively transferred A-NK and T-LAK cells

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