Gene-modified tumor cells

Another strategy to treat tumors by stimulation of the immune system is to use cell-based therapies [86]. In addition to several therapies based on cytotoxic T-cells (e.g., adoptive T-cell therapy [87] or tumor-loaded, activated DCs [88]), one important approach is the use of gene-modified tumor cells. Cell-based tumor therapies can be divided into either autologous and allo-genous strategies ... 

The first-generation therapies of gene-modified tumor cells used either GM-CSF or IL-2 as the immune stimulating molecule [89]. Several tumor models in animals, as well as clinical trials with tumor patients, have shown promising results, but further intensification of the induced immune response appears to be necessary [90, 91]. 

Antonia, S.J. (1999) B7-1 gene-modified tumor cell vaccines. Curr Opin Mol Ther 1 50-56. 

Parmiani G, Rodolfo M, Melani C. Immunological gene therapy with ex vivo gene-modified tumor cells a eritique and a reappraisal. Hum Gene Ther 2000 11 1269-1275. 

To prevent tumor growth, gene-modified BM185 cells were used as a vaccine. BM185 cells were double transfected with the co-stimulatory molecule CD80/B7.1 and the cytokine GM-CSF, both encoded... 

Fakhrai H, Mantil JC, Liu L, Nicholson GL, Murphy-Satter CS, Ruppert J et al. Phase I chnical trial of a TGF-beta antisense-modified tumor cell vaccine in patients with advanced ghoma. Cancer Gene Ther 2006 13 1052-1060. 

Miller PW, Sharma S, Stolina M, et al. Intratumoial administration of adenoviral interleukin 7 gene-modified derrdritic cells augments specific antitirmor immutrity and achieves tumor eradication. Hum Gene Ther 2000 11 53-65. 

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 incidence of ovarian tumors in mice, guinea pigs, and rabbits increased after 3 years of chronic irradiation at doses as low as 1.1 mGy daily (Lorenz et al. 1954). Unlike other tumors, the induction of ovarian tumors depended on a minimum total dose and seemed to be independent of a daily dose (Lorenz et al. 1954). Radiation-induced neoplastic transformation of hamster cells may be associated initially with changes in expression of the genes modifying cytoskeletal elements (Woloschak et al. 1990b). 

For non-suspension cultures, suitable matrices include liquid overlay on agarose (59), Matrigel , or Cultrex (48, 92). More recently, micropatterned arrays have been developed for adherent 3-D spheroid cultures (56) and have been used to show reduced chemosensitivity of colorectal carcinoma cells to irinotecan (58). In some cases, 3-D cultures can be enhanced by the addition of host cells. This increases complexity, but inevitably decreases flexibility and speed of analysis. However, important insights into the role of host cells have emerged stromal cells modify the gene expression and response of many tumor cell types to chemotherapeutic agents (93) and tumor-associated myofibroblasts can enhance tumor invasiveness (94). 

Immunization of Cancer Patients Using Autologous Cancer Cells Modified by Insertion of the Gene for Tumor Necrosis Factor (TNF)... 

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