Activation of host antitumoral responses by cationic lipid/DNA complexes

Bramson, Jonathan L.; Bodner, Carolyn A.; Graham, Roger W.

doi:10.1038/sj.cgt.7700143

Cited by 31 publications

(19 citation statements)

References 16 publications

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“…There have been numerous reports of intravenous administration of synthetic vectors containing bacterially derived DNA inciting the production of cytokines such as TNF-a , IFN-c and interleukin-12 (Dow et al 1999;Li et al 1999;Tan et al 1999;Whitmore et al 1999;Bramson et al 2000).…”

Section: Loss Of Gene Expression Owing To Lipoplexmediated Enhanced Imentioning

confidence: 99%

Cytotoxicity issues pertinent to lipoplex-mediated gene therapy in-vivo

Dass

2002

Journal of Pharmacy and Pharmacology

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Cationic liposomes bind with nucleic acids such as plasmids and oligodeoxynucleotides to form complexes known as lipoplexes. Although these lipoplexes have several advantages over other forms of nucleic acid transfer methods in cell culture and in-vivo, toxicity remains a problem, especially in-vivo. Nevertheless, these carriers have been used in clinical trials against cystic brosis and cancer and their usage is attributed mainly to their versatility, especially when it comes to the range of routes available for administration of nucleic-acid-based drugs in-vivo.

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Section: Loss Of Gene Expression Owing To Lipoplexmediated Enhanced Imentioning

confidence: 99%

Cytotoxicity issues pertinent to lipoplex-mediated gene therapy in-vivo

Dass

2002

Journal of Pharmacy and Pharmacology

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“…Statistical significance between treated groups and control groups was determined by one-way ANOVA analysis (***Po0.001; **Po0.005; *Po0.01; not significant (ns) P40.05). 56 It has also been reported that the CpG motifs present in the DNA are responsible for the immunostimulatory effect, since the methylation or elimination of these motifs resulted in a reduction of cytokine production. [57][58][59] These findings may explain the delay in the tumor growth observed when mice were injected with Tf-lipoplexes carrying the b-galactosidase gene (Figure 2a) The microenvironment of the tumors was also altered in treated animal groups.…”

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confidence: 99%

Transferrin lipoplex-mediated suicide gene therapy of oral squamous cell carcinoma in an immunocompetent murine model and mechanisms involved in the antitumoral response

et al. 2008

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Suicide gene therapy has been used for the treatment of a variety of cancers. We reported previously the in vitro efficacy of the Herpes Simplex Virus Thymidine kinase (HSV-tk)/ganciclovir (GCV) system to mediate cytotoxicity in oral squamous cancer cells, using transferrin (Tf)-lipoplexes, prepared from cationic liposomes composed of 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP) and cholesterol. In the present study, we evaluated the antitumoral efficacy mediated by this lipoplex formulation in two suicide gene therapy strategies, HSV-tk/GCV and cytosine deaminase (CD)/5-fluorocytosine (5-FC), using a syngeneic, orthotopic murine model for head and neck squamous cell carcinoma. The cellular and molecular events associated with the antitumoral response elicited by both the therapeutic approaches were investigated by analyzing tumor cell death, tumor-infiltrating immune cells and tumor cytokine microenvironment. Significant tumor reduction was achieved upon intratumoral delivery of HSV-tk or CD genes mediated by Tf-lipoplexes, followed by intraperitoneal injection of GCV or 5-FC, respectively. Enhanced apoptosis, the recruitment of NK cells, CD4 and CD8 T-lymphocytes and an increase in the levels of several cytokines/chemokines were observed within the tumors. These observations suggest that suicide gene therapy with lipoplexes modifies the tumor microenvironment, and leads to the recruitment of immune effector cells that can act as adjuvants in reducing the tumor size.

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“…When combined with the cytostatic drug cisplatin, the c-myc antisense molecules encapsulated within SALPs resulted in a prolonged downregulation of c-myc in vivo, reduced tumour progression, and increased the median survival of mice in comparison to placebo-treated mice. Finally, as mentioned below, SALPs can be used to enhance immunostimulation in vivo mediated by foreign nucleic acids (Bramson et al 2000;Mui et al 2001). The immunogenicity of the immunostimulatory sequence is not only enhanced by encapsulation in SALPs, but enables even unmodified (phosphodiester, PO) sequences to act as immunostimulants (Mui et al 2001).…”

mentioning

confidence: 99%

Immunostimulatory activity of cationic-lipid-nucleic-acid complexes against cancer

2002

Journal of Cancer Research and Clinical Oncology

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Recent studies have highlighted the immunostimulatory nature of nucleic acids and the enhancement of such immunostimulation when nucleic acids are complexed to cationic liposomes to form cationic-lipid-nucleic-acid-complexes or lipoplexes. While such immunostimulation may have deleterious consequences for nucleic acid delivery, especially in the field of gene therapy, it may be harnessed for efficacious usage against the various forms of cancer.

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Activation of host antitumoral responses by cationic lipid/DNA complexes

Cited by 31 publications

References 16 publications

Cytotoxicity issues pertinent to lipoplex-mediated gene therapy in-vivo

Cytotoxicity issues pertinent to lipoplex-mediated gene therapy in-vivo

Transferrin lipoplex-mediated suicide gene therapy of oral squamous cell carcinoma in an immunocompetent murine model and mechanisms involved in the antitumoral response

Immunostimulatory activity of cationic-lipid-nucleic-acid complexes against cancer

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