Tumor transfection

Dow, S.W., Elmslie, R.E., Willson, A.P., Roche, L., Gorman, C. and Potter, T.A. (1998)In vivo tumor transfection with superantigen plus cytokine genes induces tumor regression and prolongs survival in dogs with malignant melanoma. J. Clin. Invest., 101, 2406-2414. 

While the applications of SELP-mediated controlled gene delivery are numerous, we have focused our efforts on controlled delivery to solid tumors. Our initial studies in this arena involved the intratumoral delivery of a reporter plasmid Renilla luciferase) to solid tumors in a murine (athymic nu/nu) model of human breast cancer (MDA-MB-435 cell line) (50). Delivery of the Renilla luciferase plasmid from SELP-47K matrices resulted in significantly enhanced tumor transfection for up to 21 days compared to naked DNA (Fig. 5). In particular, delivery of the plasmid from matrices containing 4 or 8 wt.% polymer resulted in enhanced transfection... 

The levels of tumor transfection mediated by the three concentrations of polymer were statistically equivalent until 7 days, when the 4 and 8 wt.% matrices were both more effective than 12 wt.%. The greater transfection persisted until 21 days for 4 wt.% polymer and 14 days for 8 wt.% poljnner. Overall, the delivery of DNA from 4, 8, and 12 wt.% hydrogels resulted in a mean 142.4-fold, 28.7-fold, and 3.5-fold increase in tumor transfection, respectively, compared with naked DNA over the entire 28 day period. 

Lukacs, K.V., Lowrie, D.B., Stokes, R.W., Colston, M.J. (1993). Tumor cells transfected with a bacterial heat shock gene lose tumorigenicity and induce protection against tumors. J. Exp. Med. 178,343-348. 

The neoangiogenic tumor vasculature overexpresses certain integrins and other surface markers, which can also be used for targeting of polyplexes. The RGD peptide motif has been successfully applied for integrin-targeted pDNA [125-128] and siRNA [129, 130] delivery. In many cases, the PEG motif-containing peptide was attached to the polycation via a PEG spacer. For RGD-PEG-PEI/pDNA polyplexes, an optimum grafting with RGD-PEG was required because transfection... 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

The administration of SPLP results in reporter gene expression at the tumor site (Fig. 7B). Injection of free plasmid or lipoplexes resulted in no detectable gene expression at the tumor site. However, transfection was observed in the limg, liver, and spleen. SPLP, on the other hand, did not show detectable levels of gene expression in these organs. 

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