Cancer gene transfer studies

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],... 

Schuler M, Rochlitz C, Horowitz JA, et al. A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer. Hum Gene Ther 1998 9(14) 2075-2082. 

Gene transfer of mouse and human CD34+ HSCs, which were genetically modified by a retroviral virus encoding ADA cDNA and the neomycin-resistance marker gene, have been extensively characterized in mouse models without reports of toxicity. Furthermore, none of the preclinical studies for ADA-SCID have demonstrated evidence of cancer in animals treated with this same gene transfer approach [515137], [666652], [666655]. 

Clark, P.R., Stopeck, A T., Ferrari, M., Parker, S.E. and Hersh, E.M. (2000) Studies of direct intratumoral gene transfer using cationic lipid-complexed plasmid DNA. Cancer Gene Ther., 7, 853-860. 

A single clinical trial using wild-type p53 gene transfer in nine patients with non-small cell lung cancer in whom conventional treatment had failed has been reported. In this study, the LNSX retroviral vector was injected di-... 

Stopeck AT, Jones A, Hersh EM, Thompson JA, Einucane DM, GutheH JC, Gonzalez R. Phase II study of direct intralesional gene transfer of aUovectin-7, an HLA-B7/beta2-microglobulin DNA-Uposome complex, in patients with metastatic melanoma. Clin Cancer Res. 2001 7(8) 2285-91. 

Cancer Gene Therapy. 1994-. London, U.K/ Nature Publishing. Monthly. ISSN 0929-1903. URL http //www.nature.com/ cgt/. Presents results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy as applied to cancer research, case reports, preliminary communications, review articles, and industry perspectives (descriptions of the newest technology being developed in the corporate sector). 

Rat and human NIS was cloned and characterized in 1996. One of the approaches to increase the expression of NIS is gene transfer. Many studies have investigated the effect of NIS transfer on radioiodine therapy (Lee et al., 2004 Spitzweg et al., 2003), and NIS transfection via a viral vector has been shown to induce iodide uptake in several human nonthyroid tumor cell lines and xenografts, including gliomas, prostate cancer, ovarian cancer and colon cancer (Mandell et al., 1999 Cho et al., 2000). 

Tagawa S T, Lee P, Snively J, et al. (2003). Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma. Cancer. 98 144-154. Prud homme G J, Glinka Y, Khan A S, et al. (2006). Electroporation-enhanced non-viral gene transfer for the prevention or treatment of immunological, endocrine and neoplastic diseases. Curr. Gene. Ther. 6 243-273. 

Investigators submitting human gene transferproposals must include the Informed Consent document as approved by the local Institutional Review Board. A separate Informed Consent document should be used forthe gene transfer portion of a research project when gene transfer is used as an adjunct in the study of another technique, e.g., when a gene is used as a marker or to enhance the power of immunotherapy for cancer. 

Schuler M, Herrmann R, De Greve JL, Stewart AK, Gatzemeier U, Stewart DJ, Laufman L, Gralla R, KubaU J, Buhl R, Heussel CP, Kommoss F, Perruchoud AP, Shepherd FA, Fritz MA, Horowitz JA, Huber C, Rochlitz C. Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-smaU-ceU lung cancer results of a multicenter phase II study. J Clin Oncol 2001 19 1750-1758. 

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