Biodegradable polymer-based interleukin-12 gene delivery: role of induced cytokines, tumor infiltrating cells and nitric oxide in anti-tumor activity

Maheshwari, Anurag; Han, Sang-oh; Mahato, Ram I.; Kim, S. W.

doi:10.1038/sj.gt.3301766

Cited by 50 publications

(26 citation statements)

References 34 publications

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“…The particle size of PDBA/pDNA complex was about 200 nm. This is smaller than that of cationic liposome complexes (11357235 nm), 24 but larger than that of PAGA (100 nm) 18 or WSLP (26-62 nm). 19 In our preliminary experiments, the size can be decreased to 100 nm, when the complex was prepared in MQ water (not in PBS).…”

Section: Discussionmentioning

confidence: 66%

“…Furthermore, nonviral vectors may be good clinical options because they may be more efficient and less labor intensive than viral vectors, although the present gene transfection efficiencies still need to be improved. Recently, nonviral gene delivery systems with polyvinylpyrrolidone (PVP), 16 poly[a-(4-aminobutyl)-L-glycolic acid] (PAGA), 17,18 and water-soluble lipopolymers (WSLP) 19 have been developed and reported. However, the best method for intratumoral delivery of the IL-12 gene remains to be determined.…”

mentioning

confidence: 99%

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Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

et al. 2003

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Delivery of the interleukin-12 (IL-12) gene to solid tumors is a promising anticancer therapy. Vectors are currently being developed to achieve safe and effective intratumoral delivery of the IL-12 gene. Poly [D,L-2,4-diaminobutyric acid] (PDBA) is a novel gene carrier that was recently described. The goal of this study was to use this gene delivery system for treatment of solid tumors. To determine the optimal conditions for transfection, established B16F10-melanomas in C57BL/6 mice were treated with intratumoral injection of the PDBA/plasmid luciferase (pLuc) complex. We determined that the optimal complex composition was 50 mg/ml pLuc and 150 mg/ml PDBA. High levels of IL-12 protein were expressed in tumors after a single injection of PDBA/murine IL-12 (pmIL-12) complex, whereas serum levels of IL-12 in treated mice were below the limits of detection. IL-12 gene therapy with the PDBA system significantly inhibited tumor growth in comparison with the controls (Po.001). Moreover, both natural killer and cytotoxic T lymphocyte activities from draining lymph nodes of PDBA/pmIL-12-treated mice were increased substantially in comparison with those of controls (Po.05). These results suggest that PDBA-mediated IL-12 gene therapy is a potential strategy for treatment of patients with solid tumors.

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Section: Discussionmentioning

confidence: 66%

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confidence: 99%

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

et al. 2003

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“…46 The islet samples were used for glucose-stimulated insulin release. 19 There was no increase in NO release in the presence of these cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…At 12 h post-transfection, islets were washed and incubated at 371C with 500 Units/ml each of TFN-a and IFN-g. At days 5 and 10, 1 ml of the culture supernatants was collected from each well for assays of nitric oxide (NO) in terms of nitrite (NO 2 À ) using the Griess Reagent System. 46 The islet samples were used for determining glucosestimulated insulin release. 19 …”

Section: Cytoprotective Effect Of Hvegfmentioning

confidence: 99%

Adenovirus-based vascular endothelial growth factor gene delivery to human pancreatic islets

et al. 2004

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Islet transplantation is limited by islet graft failure due to poor revascularization, host immune rejection and nonspecific inflammatory response. Delivery of human vascular endothelial growth factor (hVEGF) gene to the islets is likely to promote islet revascularization and survival. We used a bicistronic adenoviral vector encoding hVEGF and CpG-free allele of green fluorescent protein (Adv-GFP-hVEGF) and introduced into human pancreatic islets by transfection. We found that transfection efficiency and apoptosis were dependent on the multiplicity of infection (MOI). Compared to Adv-GFP transfected and nontransfected islets, the levels of hVEGF secreted from Adv-GFP-hVEGF transfected islets were higher and exhibit a linear relationship between hVEGF expression and MOI (10-5000). Persistent, but low level expression of hVEGF from nontransfected islets was also observed. This may be due to expression of the endogenous hVEGF gene under hypoxic conditions. The levels of DNA fragmentation determined by ELISA of islet lysates were dependent on the MOI of Adv-GFP-hVEGF. On glucose challenge, insulin release from transfected islets was comparable to nontransfected islets. Immunohistochemical staining for hVEGF was very high in Adv-GFP-hVEGF transfected islets. Weak staining was also observed for hCD31 in both transfected and nontransfected islets. These findings suggest that Adv-GFP-hVEGF is a potential candidate for promoting islet revascularization.

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“…Others, such as promoting the proliferation of T cells, NK cells and tumor-infiltrating lymphocytes were involved. In addition to developing strong anti-tumor CTL responses, the augmented production of other cytokines including IFN-γ, and TNF-α induced by IL-12 has been implicated in its anti-tumor effectors (6). Whereas, administration of IL-12 protein was directly limited by severe toxicity in vivo.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-12 Gene Modification Exerts Anti-Tumor Effects on Murine Mammary Sarcoma Cell Line in vivo

et al. 2008

Cell Mol Immunol

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Biodegradable polymer-based interleukin-12 gene delivery: role of induced cytokines, tumor infiltrating cells and nitric oxide in anti-tumor activity

Cited by 50 publications

References 34 publications

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

Adenovirus-based vascular endothelial growth factor gene delivery to human pancreatic islets

Interleukin-12 Gene Modification Exerts Anti-Tumor Effects on Murine Mammary Sarcoma Cell Line in vivo

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