A non-coding cationic lipid DNA complex produces lasting anti-leukemic effects

Keasey, Nikki; Herse, Zachary; Chang, Stella; Liggitt, Denny; Lay, Marla; Fairman, Jeff; Claxton, David F.

doi:10.4161/cbt.10.6.12653

Cited by 6 publications

(14 citation statements)

References 30 publications

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“…42,43 Furthermore, as previously mentioned, the 32Dp210-GFP CML model behaves like AML in vivo with its rapid onset and proliferation of immature leukemic blasts. 2,43 LSC-targeted ICG-CPSNP PDT, initiated by systemic injection of CPSNPs followed by near-infrared-irradiation of the spleen, evoked a robust antileukemic effect evident by the absence of GFP þ leukemic cells in the blood (Figure 8). This blockade of leukemic cell proliferation in vivo correlated with a profound and dramatic extension in survival ( Figure 9).…”

Section: Articlementioning

confidence: 81%

Targeted Indocyanine-Green-Loaded Calcium Phosphosilicate Nanoparticles for In Vivo Photodynamic Therapy of Leukemia

et al. 2011

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Leukemia is one of the most common and aggressive adult cancers, as well as the most prevalent childhood cancer. Leukemia is a cancer of the hematological system and can be divided into a diversity of unique malignancies based on the onset of the disease as well as the specific cell lineages involved. Cancer stem cells, including recently identified leukemia stem cells (LSCs), are hypothesized to be responsible for cancer development, relapse, and resistance to treatment, and new therapeutics targeting these cellular populations are urgently needed. Nontoxic and nonaggregating calcium phosphosilicate nanoparticles (CPSNPs) encapsulating the near-infrared fluoroprobe indocyanine green (ICG) were recently developed for diagnostic imaging and drug delivery as well as for photodynamic therapy (PDT) of solid tumors. Prior studies revealed that specific targeting of CPSNPs allowed for enhanced accumulation within breast cancer tumors, via CD71 targeting, or pancreatic cancer tumors, via gastrin receptor targeting. In the present study, ICG-loaded CPSNPs were evaluated as photosensitizers for PDT of leukemia. Using a novel bioconjugation approach to specifically target CD117 or CD96, surface features enhanced on leukemia stem cells, in vitro ICG-CPSNP PDT of a murine leukemia cell line and human leukemia samples were dramatically improved. Furthermore, the in vivo efficacy of PDT was dramatically enhanced in a murine leukemia model by utilizing CD117-targeted ICG-CPSNPs, resulting in 29% disease-free survival. Altogether, this study demonstrates that leukemia-targeted ICG-loaded CPSNPs offer the promise to effectively treat relapsing and multidrug-resistant leukemia and to improve the life of leukemia patients.

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Section: Articlementioning

confidence: 81%

Targeted Indocyanine-Green-Loaded Calcium Phosphosilicate Nanoparticles for In Vivo Photodynamic Therapy of Leukemia

et al. 2011

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“…80 JVRS-100's efficacy has been proven in preclinical studies as a means to stimulate the immune system to fight against leukemias. 81 Considering that nanoparticles are more often designed to avoid immune system and/or complement activation, the methodology behind delivery system is less intuitive; however, it is clear that JVRS-100 is designed to utilize key features of nanoparticles, notably their uptake by the reticulo-endothelial system and abilities to encapsulate and protect DNA, to act as an ideal system for immune system activation. Other systems ( 188 Re-BMEDA-liposome) are incorporating radioactive isotopes into liposomes as a means to target the delivery of the radionuclides to tumors.…”

Section: Gene Therapymentioning

confidence: 99%

“…This is done via the CpG motifs contained in the DNA in combination with adjuvant effects from the liposome . JVRS‐100's efficacy has been proven in preclinical studies as a means to stimulate the immune system to fight against leukemias . Considering that nanoparticles are more often designed to avoid immune system and/or complement activation, the methodology behind delivery system is less intuitive; however, it is clear that JVRS‐100 is designed to utilize key features of nanoparticles, notably their uptake by the reticulo‐endothelial system and abilities to encapsulate and protect DNA, to act as an ideal system for immune system activation.…”

Section: Current Nanoparticle/microparticle Clinical Trialsmentioning

confidence: 99%

Nanoparticles in the clinic

Anselmo

Mitragotri

2016

Bioengineering & Transla Med

1,113

603

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Nanoparticle/microparticle‐based drug delivery systems for systemic (i.e., intravenous) applications have significant advantages over their nonformulated and free drug counterparts. For example, nanoparticle systems are capable of delivering therapeutics and treating areas of the body that other delivery systems cannot reach. As such, nanoparticle drug delivery and imaging systems are one of the most investigated systems in preclinical and clinical settings. Here, we will highlight the diversity of nanoparticle types, the key advantages these systems have over their free drug counterparts, and discuss their overall potential in influencing clinical care. In particular, we will focus on current clinical trials for nanoparticle formulations that have yet to be clinically approved. Additional emphasis will be on clinically approved nanoparticle systems, both for their currently approved indications and their use in active clinical trials. Finally, we will discuss many of the often overlooked biological, technological, and study design challenges that impact the clinical success of nanoparticle delivery systems.

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“…Furthermore, in vivo evidence suggests that the induction of a strong T H 1-type immune response is based in part by activation of cytolytic T lymphocytes (CTLs) and natural killer (NK) cells and production of interleukin (IL) 12 (IL-12) and type I and II interferons [ 20 – 22 ] all of which are known to be important mediators of antitumor immunity. JVRS-100 administered in combination with tumor cell lysates has efficacy against tumor progression in mouse models of cancer and in dogs with naturally-occurring tumors and increased survival in these animal models [ 23 – 25 ]. Furthermore, the combination of JVRS-100 with antigen resulted in a potent adjuvant effect as well as in robust antibody and CTL responses to the target antigen.…”

Section: Introductionmentioning

confidence: 99%

Prevention of liver tumor formation in woodchucks with established hepatocellular carcinoma by treatment with cationic liposome-DNA complexes

2017

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BackgroundApproximately 250 million people worldwide are chronically infected with hepatitis B virus (HBV) and more than half of the hepatocellular carcinoma (HCC) cases are attributed to this infection. As HCC has a high mortality rate, and current treatment options are remarkably limited, the development of new therapeutic treatment strategies is warranted.MethodsIn this study, woodchucks infected with woodchuck hepatitis virus (WHV), and with pre-existing liver tumors, were used as a model to investigate if complexes of cationic liposomes and non-coding DNA (JVRS-100) were effective in treatment of HCC.ResultsIt was observed that the high serum viral load that is present in a typical chronic WHV infection (i.e., approximately 100-fold higher than human viral loads) results in immune suppression and resistance to treatment with JVRS-100. Treatment of woodchucks with lower serum viral load that more closely matched with the viral load usually seen in human HBV infection appears a better model for immunotherapeutic development based on the responsiveness to JVRS-100 treatment. In the latter case, marked declines in WHV DNA and WHV surface antigen were determined over the 12-week treatment period and WHV markers stayed suppressed during most time points of the 12-week follow-up period. Even more remarkably, the formation of new liver tumors was not observed in woodchucks treated with a well-tolerated dose of JVRS-100, as compared to several new tumors that developed in vehicle-treated control animals.ConclusionsAlthough there was little decrease in the volumes of the liver tumors existing at the time of treatment, it is generally accepted that preventing the spread and metastasis of almost always fatal cancers such as HCC and thus, reducing it to a chronic and treatable disease can also be a successful therapeutic approach. The results in woodchucks warrant the investigation of JVRS-100 as an intervention to prevent liver cancer in patients chronically infected with HBV and at high risk for HCC development.

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A non-coding cationic lipid DNA complex produces lasting anti-leukemic effects

Cited by 6 publications

References 30 publications

Targeted Indocyanine-Green-Loaded Calcium Phosphosilicate Nanoparticles for In Vivo Photodynamic Therapy of Leukemia

Targeted Indocyanine-Green-Loaded Calcium Phosphosilicate Nanoparticles for In Vivo Photodynamic Therapy of Leukemia

Nanoparticles in the clinic

Prevention of liver tumor formation in woodchucks with established hepatocellular carcinoma by treatment with cationic liposome-DNA complexes

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