Tumor-targeted delivery of biologically active TRAIL protein

Zhang, H. Y.; Man, Jiang Hong; Liang, Bin; Zhou, Tao; Wang, Chenhui; Li, T.; Li, H. Y.; Li, W. H.; Jin, Bilian; Zhang, P. J.; Zhao, Jeffrey; Pan, Xin; He, Kun; Gong, Weili; Zhang, X. M.; Li, A. L.

doi:10.1038/cgt.2009.76

Cited by 36 publications

(20 citation statements)

References 38 publications

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“…Past preclinical studies and clinical trials have focused on delivery of TRAIL variants to treat solid tumors, rather than metastatic cells within the bloodstream [28,29]. In fact, CTCs are mostly valued as predictors of disease progression rather than a bottleneck of metastasis that are available for targeting.…”

Section: Discussionmentioning

confidence: 99%

TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer

Wayne

Chandrasekaran

Mitchell

et al. 2016

Journal of Controlled Release

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Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood, both in human blood samples and in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells. We conclude that the use of circulating leukocytes as a carrier for the anti-cancer protein TRAIL could be an effective tool to directly target circulating tumor cells for the prevention of prostate cancer metastasis, and potentially other cancers that spread through the bloodstream.

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Section: Discussionmentioning

confidence: 99%

TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer

Wayne

Chandrasekaran

Mitchell

et al. 2016

Journal of Controlled Release

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“…Many of the genes that could be used to aggressively promote cancer cell apoptosis or stimulate an immune response to a tumor will result in unacceptable toxicity if delivered primarily to the lungs and liver [12, 13]. Two cytokines that have been shown to deter metastasis and effectively treat already established metastases are IL-12 and IL-2 [14-16].…”

Section: Introductionmentioning

confidence: 99%

“…Other attractive genes for delivery encode ligands that target death receptors leading to apoptosis, including tumor necrosis factor-alpha (TNF-alpha), CD95/FAS and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) [13, 18, 19]. The appeal of a suicide protein being delivered to tumor cells is undeniable, but as with immune-stimulating cytokines, the non-specific systemic delivery of a suicide gene is not well tolerated [20].…”

Section: Introductionmentioning

confidence: 99%

Systemic tumor-specific gene delivery

Kullberg¹,

McCarthy²,

Anchordoquy³

2013

Journal of Controlled Release

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The objective of a systemically administered cancer gene therapy is to achieve gene expression that is isolated to the tumor tissue. Unfortunately, viral systems have strong affinity for the liver, and delivery from non-viral cationic systems often results in high expression in the lungs. Non-specific delivery to these organs must be overcome if tumors are to be aggressively treated with genes such as IL-12 which activates a tumor immune response, and TNF-alpha which can induce tumor cell apoptosis. Techniques which have led to specific expression in tumor tissue include receptor targeting through ligand conjugation, utilization of tumor specific promoters and viral mutation in order to take advantage of proteins overexpressed in tumor cells. This review analyzes these techniques applied to liposomal, PEI, dendrimer, stem cell and viral gene delivery systems in order to determine the techniques that are most effective in achieving tumor specific gene expression after systemic administration.

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“…Bacteria have also been engineered to express anticancer agents for targeted delivery to tumors 8, 16–17 . Salmonella typhimurium , strains SL1344 18 and VNP20009 8, 14, 19 , and Escherichia coli , strains K12 20 and DH5α 21 , are facultative anaerobic enteric bacteria with well-studied and easily modifiable genetics that have previously been evaluated as anti-cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

Motility is critical for effective distribution and accumulation of bacteria in tumor tissue

Toley

Forbes

2011

Integrative Biology

122

106

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Motile bacteria can overcome the penetration limitations of cancer chemotherapeutics because they can actively migrate into solid tumors. Although several genera of bacteria have been shown to accumulate preferentially in tumors, the spatiotemporal dynamics of bacterial tumor colonization and their dependence on bacterial motility is not clear. For effective tumor regression, bacteria must penetrate and distribute uniformly throughout tumors. To measure these dynamics, we used an in vitro model of continuously perfused tumor tissue to mimic the delivery and systemic clearance of Salmonella typhimurium strains SL1344 and VNP20009, and Escherichia coli strains K12 and DH5α. Tissues were treated for 1 hour with 105 or 107 CFU/ml suspensions of each strain and the location and extent of bacterial accumulation was observed for 30 hours. Salmonella had 14.5 times greater average swimming speeds than E.coli and colonized tissues at 100 times lower doses than E.coli. Bacterial motility strongly correlated (R2 = 99.3%) with the extent of tissue accumulation. When inoculated at 105 CFU/ml, motile Salmonella formed colonies denser than 1010 CFU/(g-tissue) and less motile E.coli showed no detectable colonization. Based on spatio-temporal profiles and a mathematical model of motility and growth, bacterial dispersion was found to be necessary for deep penetration into tissue. Bacterial colonization caused apoptosis in tumors and apoptosis levels correlated (R2 = 98.6%) with colonization density. These results show that motility is critical for effective distribution of bacteria in tumors and is essential for designing cancer therapies that can overcome the barrier of limited tumor penetration.

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Tumor-targeted delivery of biologically active TRAIL protein

Cited by 36 publications

References 38 publications

TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer

TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer

Systemic tumor-specific gene delivery

Motility is critical for effective distribution and accumulation of bacteria in tumor tissue

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