Cancer and gene therapy

Schmidt-Wolf, Gabriele; Schmidt‐Wolf, Ingo G.H.

doi:10.1007/s002770050231

Cited by 8 publications

(5 citation statements)

References 48 publications

(60 reference statements)

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“…We have formulated our nanospheres with the necessary size for endocytosis, which results in an intracellular delivery of pDNA that increases transfection efficiency by avoiding enzyme degradation in the circulation . In order to be endocytosed, the nanospheres must mimic the scale of viruses by being less than 1 μm in diameter.…”

Section: Discussionmentioning

confidence: 99%

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Nanospheres Formulated from l-Tyrosine Polyphosphate Exhibiting Sustained Release of Polyplexes and In Vitro Controlled Transfection Properties

et al. 2009

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Currently, viruses are utilized as vectors for gene therapy, since they transport across cellular membranes, escape endosomes, and effectively deliver genes to the nucleus. The disadvantage of using viruses for gene therapy is their immune response. Therefore, nanospheres have been formulated as a nonviral gene vector by blending l-tyrosine-polyphosphate (LTP) with polyethylene glycol grafted to chitosan (PEG-g-CHN) and linear polyethylenimine (LPEI) conjugated to plasmid DNA (pDNA). PEG-g-CHN stabilizes the emulsion and prevents nanosphere coalescence. LPEI protects pDNA degradation during nanosphere formation, provides endosomal escape, and enhances gene expression. Previous studies show that LTP degrades within seven days and is appropriate for intracellular gene delivery. These nanospheres prepared by water-oil emulsion by sonication and solvent evaporation show diameters between 100 and 600 nm. Also, dynamic laser light scattering shows that nanospheres completely degrade after seven days. The sustained release of pDNA and pDNA-LPEI polyplexes is confirmed through electrophoresis and PicoGreen assay. A LIVE/DEAD cell viability assay shows that nanosphere viability is comparable to that of buffers. X-Gal staining shows a sustained transfection for 11 days using human fibroblasts. This result is sustained longer than pDNA-LPEI and pDNA-FuGENE 6 complexes. Therefore, LTP-pDNA nanospheres exhibit controlled transfection and can be used as a nonviral gene delivery vector.

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Section: Discussionmentioning

confidence: 99%

“…In contrast, synthetic biodegradable polymers can provide a sustained transfection by degrading and releasing pDNA at controlled rates . These vectors can decrease the number of doses and maintain optimum dosage levels for gene expression .…”

Section: Introductionmentioning

confidence: 99%

Nanospheres Formulated from l-Tyrosine Polyphosphate Exhibiting Sustained Release of Polyplexes and In Vitro Controlled Transfection Properties

et al. 2009

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“…Retrovirus-mediated gene transfer is currently the method of choice for transfection of human T lymphocytes. Viral vectors, however, require dividing target cells (except for DNA-viruses such as adenoviruses) and may raise safety questions in human gene therapy (Schmidt-Wolf et al, 1996). CD3 receptor-mediated gene transfer is an efficient method for the transfection of CIK cells and cell mortality is relatively low, compared to other nonviral gene transfer methods (Buschle et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma

et al. 1999

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Summary Natural killer-like T lymphocytes termed cytokine-induced killer (CIK) cells have been shown to eradicate established tumours in a severe combined immune deficient (SCID) mouse/human lymphoma model. Recently, we demonstrated that CIK cells transfected with cytokine genes possess an improved proliferation rate and a significantly higher cytotoxic activity as compared to non-transfected cells. Here, in a phase I clinical protocol, autologous CIK cells were generated from peripheral blood obtained by leukapheresis in patients with metastatic renal cell carcinoma, colorectal carcinoma and lymphoma. CIK cells were transfected with a plasmid containing the interleukin-2 (IL-2) gene via electroporation. Transfected cells generated IL-2 in the range of 330-1800 pg 10 -6 cells 24 h -1 with a mean of 836 pg 10 -6 cells 24 h -1. Ten patients received 1-5 intravenous infusions of IL-2-transfected CIK cells; five infusions with transfected CIK cells were given. In addition, the same patients received five infusions with untransfected CIK cells for control reasons. In three patients, WHO grade 2 fever was observed. Based on polymerase chain reaction of peripheral blood transfected cells could be detected for up to 2 weeks after infusion. There was a significant increase in serum levels of interferon gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor beta (TGF-β) during treatment. Interestingly, there was also an increase in CD3+ lymphocytes in the blood of patients during therapy. In accordance, a partial increase in cytotoxic activity in peripheral blood lymphocytes (PBLs) was documented when patient samples before and after therapy were compared. Concerning clinical outcome, six patients remained in progressive disease, three patients showed no change by treatment, and one patient with lymphoma developed a complete response. In conclusion, we were able to demonstrate that CIK cells transfected with the IL-2 gene can be administered without major side-effects and are promising for future therapeutic trials.

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“…Cytokine genes have been used in most instances to enhance tumour immunogenicity (Schmidt-Wolf and Schmidt-Wolf, 1996). DC are attractive targets of gene transfer since DC are easily accessable and since these cells seem to be sensitive to immunologic strategies.…”

Section: Transfection Into Dendritic Cellsmentioning

confidence: 99%

Generation of dendritic cell-based vaccines for cancer therapy

Reinhard¹,

Märten²,

Kiske³

et al. 2002

Br J Cancer

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Dendritic cells play a major role in the generation of immunity against tumour cells. They can be grown under various culture conditions, which influence the phenotypical and functional properties of dendritic cells and thereby the consecutive immune response mainly executed by T cells. Here we discuss various conditions, which are important during generation and administration of dendritic cells to elicit a tumouricidal T cell-based immune response.

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Cancer and gene therapy

Cited by 8 publications

References 48 publications

Nanospheres Formulated from l-Tyrosine Polyphosphate Exhibiting Sustained Release of Polyplexes and In Vitro Controlled Transfection Properties

Nanospheres Formulated from l-Tyrosine Polyphosphate Exhibiting Sustained Release of Polyplexes and In Vitro Controlled Transfection Properties

Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma

Generation of dendritic cell-based vaccines for cancer therapy

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